GENERAL  PRINCIPLES 


OF 


OKGANIC   SYNTHESES 


BY  ,;    ;     :;    , 

P.  ALEXEYEFF/     ',.,  „     — r';J 

Lot*  Professor  of  Chemistry,  University  of  Kiefi,  Ruit\a 


AUTHORIZED  TRANSLATION  WITH  REVISION  AND 
ADDITIONS 

BY 

J.  MEKKITT  MATTHEWS,  PH.D. 

Head  of  Chemical  Department,  School  of  Industrial  Art,  Philadelphia. 


FIRST    EDITION 
FIRST    THOUSAND 


NEW    YORK 

JOHN  WILEY  &   SONS 

LONDON:    CHAPMAN  &  HALL,   LIMITED* 

1906 


GENERAL 


Copyright,  1906 

BT 

J.  MEREITT  MATTHEWS 


ROBERT  DRUMMOND,  PRINTER,  NEW  TOJUt 


PREFACE. 


THE  present  volume  has  been  based  on  a  monograph  by 
Professor  P.  Alexeyeff  (of  the  University  of  Kieff),  entitled 
Methods  for  the  Transformation  of  Organic  Compounds  (MCTO^H 
IIpeBpameHiH  OprammecKHX'b  CoefliraeHift),  which  originally 
appeared  in  1889  in  Russian.  In  the  presentation  of  the 
subject  in  this  volume,  I  have  made  rather  extensive  addi- 
tions of  new  material,  together  with  a  general  rearrangement 
of  the  entire  subject-matter. 

Professor  Alexeyeff,  himself,  has  been  deceased  these  several 
years,  but  his  widow,  Madame  Alexeyeff,  has  very  kindly  given 
me  authority  to  employ  her  husband's  book  in  the  preparation 
of  the  present  volume.  I  have  also  to  thank  Madame  Alexeyeff 
for  her  kindness  in  placing  at  my  disposal  the  originals  of  her 
husband's  book  in  Russian,  which  have  been  of  very  material 
assistance  to  me  in  the  translation.  For  the  latter  purpose  I 
have  also  made  good  use  of  Darzen's  and  Lefevre's  French 
translation  of  the  original  Russian. 

This  book  is  intended  for  the  general  student  of  advanced 
organic  chemistry,  and  deals  only  with  the  theory  of  the  sub- 
ject. It  is  not  intended  in  any  way  as  a  laboratory  manual 
for  the  preparation  of  organic  compounds.  Although  there  are 
a  number  of  good  books  of  the  latter  class  available  for  the 
American  or  English  student,  yet  I  do  not  believe  there  is  any 
book  in  English  which  covers  quite  the  same  ground  as  the 

present  volume. 

iii 


IV  PREFACE. 

The  attempt  of  the  author  has  been  to  present  the  theory 
of  organic  radicals  in  a  systematic  form  and  in  as  logical  a 
method  of  development  as  possible,  so  that  the  student  may 
acquire  a  comprehensive  grasp  of  the  general  principles  under- 
lying synthetic  organic  chemistry.  General  organic  chemistry 
lias  grown  so  greatly  in  its  mass  of  detail  and  in  the  number  of 
its  isolated  reactions  and  separate  compounds  that  the  ma- 
jority of  advanced  text-books  on  the  subject  are  now  more 
like  complex  reference  encyclopedias  than  actual  books  of  in- 
struction. The  student  becomes  bewildered  in  an  attempt  to 
pick  his  way  through  the  thousands  and  thousands  of  com- 
pounds dealt  with,  and  loses  sight  of  the  underlying  path  which 
represents  the  general  principles  of  the  subject.  In  the  present 
iDook  the  author  has  endeavored  to  discuss  general  reactions  in 
as  broad  a  manner  as  possible,  though  making  use  of  specific 
reactions  for  purposes  of  illustration.  In  such  a  treatment  it 
is  possible,  of  course,  to  become  too  purely  theoretical  and  to 
make  a  few  facts  the  basis  of  too  generalized  a  reaction,  and 
I  fear  that  in  many  cases  I  have  erred  in  this  direction.  This 
book,  however,  is  intended  to  serve  merely  as  a  companion 
•volume  and  to  be  used  in  connection  with  a  general  organic 
chemistry,  and  the  latter  will  prevent  the  student  from  carrying 
too  far  the  generalizations  given  in  this  volume. 

J.  MERRITT  MATTHEWS. 

PENNSYLVANIA  MUSEUM 

AND 
SCHOOL  OF  INDUSTRIAL  ART, 

PHILADELPHIA,  March,  1906. 


CONTENTS. 


CHAPTER  I. 
OXIDATION. 

PAGE 

1.  GENERAL  CONSIDERATIONS i 

2.  ACTION  OF  OXIDIZING  AGENTS 2 

3.  DIRECT  OXIDATION 15 

A.  Oxidations  which  Preserve  the  same  Number  of  Carbon  Atoms 

in  the  Molecule 15 

B.  Direct  Oxidation  Accompanied  by  Decomposition  of  the  Mole- 

cule   29 

4.  INDIRECT  OXIDATION 35 

A.  Substitution  of  a  Halogen  by  the  Hydroxyl  Group 35 

B.  Oxidation  by  the  Use  of  Ammonia  Compounds 41 

C.  Conversion  of  the  Sulphonic  Acid  Group  into  the   Hydroxyl 

Group 45 

D.  Substitution  of  Sulphur  by,  Oxygen 46 


CHAPTER  II. 
REDUCTION. 

1.  GENERAL  CONSIDERATIONS 48 

2.  ACTION  OF  REDUCING  AGENTS 49 

3.  SUBSTITUTION  OF  HYDROGEN  FOR  HYDROXYL  OR  OTHER  ELEMENT, 

GROUP,  OR  RADICAL 51 

A.  Reduction  of  Hydroxyl  and  Ketonic  Compounds 51 

(1)  Reduction  of  Acids 51 

(2)  ' '  Aldehydes 53 

(3)  ' '  Ketones  and  Quinones 53 

(4)  "          "Alcohols 55 

v 


vi  CONTENTS. 


B.  Substitution  of  Other  Groups  by  Hydrogen 56 

(i)  Substitution  of  the  Halogens 56 

(a)            "           "    "    Nitrile  Radical 58 

(3)  "            "    "    Nitro  Group 58 

(4)  "           "    "    Nitroso  Group 58 

(5)  "           "    "   Amido  Group 58- 

(6)  "            "    "    Diazo  Group 58 

(7)  "            "    "    Sulphonic  Acid  Group 60 

(8)  "           "Oxygen 60 

(9)  "            "  Sulphur 60 

(10)  The  Removal  of  Oxygen 60 

4.  THE  FIXATION  OP  HYDROGEN 60 

5.  REDUCTION  OF  NITROSO  AND  NITRO  COMPOUNDS 63 

6.  ' '         WITH  DESTRUCTION  OF  THE  MOLECULE.  .  66 


CHAPTER  III. 
SUBSTITUTIONS. 

1.  LAWS  OF  SUBSTITUTIONS 67 

2.  SUBSTITUTION  OF  CERTAIN  ELEMENTS  OR  GROUPS  BY  OTHERS.  ......  70 

A.  Preparation  of  Halogen  Compounds 70 

B.  Exchange  of  Halogens  for  One  Another 74 

C.  Substitution  of  Other  Groups  by  Halogens 77 

D.  Preparation  of  the  Derivatives  of  Nitrous  and  Nitric  Acids  and 

of  Hydroxylamine 82 

E.  Preparation  of  Ammonia  Derivatives 93 

F.  Methods  for  Obtaining  Thio  and  Sulphur  Compounds,  and  the 

Acid  Esters  of  Sulphuric  Acid 99 

G.  Methods  for  the  Preparation  of  Metallo-organic  Derivatives.  .  106 

CHAPTER  IV. 
REMOVAL  OF  RADICALS. 

1.  GENERAL  CONSIDERATIONS 108 

2.  REMOVAL  OF  THE  HALOGENS 109 

3.  MII    HALOGEN  ACIDS 1 10 

4.  ' '  WATER 112 

5.  ' '  AMMONIA 120 

6.  ' '  HYDROGEN  SULPHIDE 120 

7.  V  SULPHURIC  ANHYDRIDE 121 

8.  ' '  CARBON 122 

9.  MONOXIDE 122 

10.  "  CARBONIC  ACID 123 

11.  "         "  FORMIC  ACID 126 


CONTENTS.  vu 

PAGE: 

12.  REMOVAL  OP  ACETIC  ACID 126 

13.  "         "A  HYDROCARBON 126 

14.  ' '         "  ALCOHOL '127 

15.  "        "  SIMPLE  ETHERS 127 

16.  "         "AMINES 127 

CHAPTER  V. 
DIRECT  FIXATION  OF  GROUPS. 

1.  GENERAL  CONSIDERATIONS 129 

2.  FIXATION  OF  HYDROGEN.  .^ 131 

3.  "          "OXYGEN 131 

4.  "         "  HALOGENS 132 

A.  Fixation  of  Chlorine 132 

B.  "        "  Bromine 133 

C.  "        "  Iodine 134 

5.  FIXATION  OF  HALOGEN  ACIDS 134 

6.  "         "WATER 135 

Fixation  of  Hydrogen  Peroxide 139 

Sulphide 139 

"        "  Sulphurous  Anhydride 1 39 

"        "  Bisulphites 139 

7.  FIXATION  OF  AMMONIA 139 

8.  "         "  OXIDES  OF  NITROGEN  AND  NITROSYL  CHLORIDE 140 

9.  "         "  HYPOCHLOROUS  ACID 141 

CHAPTER  VI. 

FIXATIONS  ACCOMPANIED  BY  A   DECOMPOSITION   OF  THE 

MOLECULE. 

1.  FIXATION  OF  WATER 143 

A.  Hydration  Followed  by  a  Rupture  of  Carbon  Bonds 143 

B.  "  "          "  "       "        "a  Bond  between  Carbon 

and  Oxygen 145 

C.  Hydration  Followed  by  a  Rupture  of  a  Bond  between  Carbon 

and  Nitrogen 147 

2.  FIXATION  OF  AMMONIA 148 

CHAPTER  VII. 
CONDENSATIONS. 

1.  CONDENSATION  BY  DIRECT  ADDITION 150 

2.  "               "  DOUBLE   DECOMPOSITION,   OR  BY  REMOVAL   OF 
GROUPS 158 

A.  Formation  of  Ethers  and  Analogous  Bodies 158 


vrn  CONTENTS. 

PAGB 

.1)  With  the  Liberation  of  a  Mineral  Acid  or  of  a  Salt 158 

(2)  Formation  of  Ethers,  etc.,  with  Liberation  of  Water 162 

(3)  ' '  Esters,    "       "  of  Ammonia . 

or  Nitrogen 164 

B.  Preparation  of  Compounds  containing  Sulphur 165 

C.  "            "          "                   "           Nitrogen 167 

(1)  Ammonia  Derivatives 167 

(a)  Derivatives  Formed  with  Liberation  of  Halogen 

Acids  or  other  Acids  or  Salts 167 

(6)  Ammonia  Derivatives  Formed  with  Liberation  of 

Water 169 

(c)  Ammonia  Derivatives  Formed  with  Liberation  of 

HaS i74 

(d)  Ammonia  Derivatives  Formed  with  Liberation  of 
NHS 175 

(2)  Derivatives  of  the  Diamines  and  the  Diimides 176 

(a)  Substituted  Hydrazines 176 

(6)  Diazo-amido  Compounds 177 

(c)  Azo  Derivatives 178 

(d)  Azoxy  Compounds 180 


CHAPTER  VIII. 
TYPES  OF  SYNTHESES. 

1.  FIXATION  OF  CARBON  MONOXIDE 182 

2.  "         "        "       DIOXIDE 183 

3.  CONDENSATION  BY  THE  TRANSFORMATION  OF  THE  CO  GROUP  INTO 

C.OH  AND  C.OX 185 

4.  CONDENSATION  WITH  Loss  OF  WATER 191 

5.  "  "        "      OF  A  HALOGEN  ACID,  OF  A  METALLOID, 

OR  OF  A  SALT 200 

•6.  CONDENSATION  WITH  LIBERATION  OF  HYDROGEN 212 

7.  "                "             "           "  WATER  AND  HYDROGEN 214 

8.  "                "             "           "  CO2 214 

9.  POLYMERIZATION 215 

CHAPTER  IX. 

ISOMERIZATION 217 


UNIVERSITY 


GENERAL  PRINCIPLES  OF 
ORGANIC    SYNTHESES- 


CHAPTER  I. 
OXIDATION. 

I.    GENERAL   CONSIDERATIONS. 

OXIDATION  is  one  of  the  most  important  reactions  in  the 
synthesis  of  organic  compounds.  The  element  carbon  has 
an  especially  strong  attraction  for  oxygen,  and  nearly  all 
organic  compounds  are  more  or  less  amenable  to  its  action, 
either  in  a  direct  or  an  indirect  manner.  The  compounds  of 
the  paraffin  series,  or,  more  properly,  the  open-chain  series,  are 
more  susceptible  to  oxidation  than  those  of  the  benzene  or 
closed-ring  series;  and  the  extent  to  which  the  oxidation  may 
be  carried  may  vary  within  considerable  limits,  the  final  limit 
in  all  cases  being  the  decomposition  of  the  molecule  into  carbon 
dioxide  and  water. 

Oxidation  may  operate  in  a  large  number  of  different  direc- 
tions, and  by  the  use  of  an  extensive  series  of  reagents.  In  a 
number  of  instances  the  exact  phase  which  the  oxidation 
assumes  will  be  dependent  upon  the  nature  of  the  reagent 
employed,1  and  many  other  conditions  of  the  reaction;  in  some 


1  When    choline  is  treated  with    concentrated  nitric  acid,  it  is  oxidized  to 
muscarine: 

0  CH.O 

OH  CH2.N(CH3)3.OH 

Choline.  Muscarine. 

But  when  treated  with  either  potassium  permanganate  or  chromic  acid  mix- 
ture,  negative  results  are  obtained. 


CH, 


2  ORGANIC  SYNTHESES. 

cases,  it  is  possible  to  direct  the  mode  and  extent  of  the  oxida- 
tion by  a  careful  selection  and  proper  regulation  of  the  various 
conditions,  and  in  this  manner  arrive  at  will  at  different  results 
from  the  same  starting-point.  In  other  cases,  the  reaction  is- 
not  so  readily  subject  to  control,  and  its  variations  may  be 
very  limited. 

The  elements  and  radicals  occurring  in  organic  compounds 
which  are  capable  of  oxidation,  in  one  manner  or  another,  are 
quite  numerous.  Carbon,  as  already  mentioned,  is  especially 
susceptible  to  the  action  of  oxygen;  so  also  is  hydrogen,  and 
to  a  less  degree  sulphur  and  nitrogen,  together  with  phosphorus 
and  the  allied  elements  which  occur  in  a  few  of  the  carbon  com- 
pounds. The  halogens  cannot  be  considered  as  oxidizable  in 
the  proper  sense  of  the  word.  The  various  metals  which  may 
occur  in  organic  combinations,  in  most  instances,  may  be  con- 
sidered as  subject  to  oxidation.  But  the  majority  of  the  re- 
actions which  have  been  carefully  studied  are  limited  to  com- 
pounds including  carbon,  hydrogen,  nitrogen,  and  sulphur  as- 
the  elements  subject  to  oxidation. 

In  the  oxidation  of  the  hydrocarbon  nucleus  (which  in. 
reality  comes  down  to  the  methyl  radical,  CHa,  as  the  unit), 
both  the  hydrogen  and  the  carbon  may  take  part  in  the  reaction.. 
Starting  with  methane,  CH4,  as  the  most  highly-reduced  com- 
pound of  carbon,  the  following  successive  stages  of  oxidation 
may  be  indicated : 

(1)  The  oxidation  of  a  single  hydrogen  atom  to  an  hydroxyl 
group: 

CH4  +  0=CH3.O.H; 

in  this  case  but  a  single  valence  of  the  carbon  atom  is  oxidized,, 
and  there  is  no  removal  of  hydrogen. 

(2)  The  removal  of  a  single  hydrogen  atom  by  oxidation  to> 
water,  and  the  formation  of  the  oxide  of  the  radical : 


OXIDATION  3 

this  reaction  may  be  considered  as  the  amplification  of  the 
foregoing  : 

2CH3.OH  -  H20  = 


(3)  The  removal  of  two  hydrogen  atoms  in  the  form  of 
water,  and  the  formation  of  an  unsaturated  compound  : 

CH2 

2  CH4+2CHI      +2H20; 
CH2 

this  reaction  may  also  be  considered  as  an  amplification  of  the 
first: 

CH3OH  CH2 

-2H20=  || 

CH3OH  CH2 

(4)  The  removal  of  two  hydrogen  atoms  in  the  form  of 
water  and  the  simultaneous  introduction  of  an  oxygen  atom  in 
their  place  : 


in  this  case,  both  the  hydrogen  and  carbon  are  oxidized;   the 
former  to  water  and  the  latter  to  the  carbonyl  group,  C  :  0,  for 


the  above  compound  is  the  aldehyde,1  H.C 


/a 
\o- 


(5)  The  oxidation  and  removal  of  two  hydrogen  atoms  as 
water,  and  the  simultaneous  oxidation  of  another  hydrogen 
atom  to  the  hydroxyl  group  and  of  the  carbon  to  the  carbonyl 
group: 

CH4+30   =H 


1  The  intermediate  reaction,  that  of  the  oxidation  of  two  hydrogen  atoms  to 
hydroxyl  groups  without  the  elimination  of  water,  does  not  appear  to  take  place, 
as  two  hydroxyl  groups  cannot  be  attached  to  the  same  carbon  atom,  a  mole- 
cule of  water  splitting  off  with  the  consequent  formation  of  a  carbonyl  group: 

CH4+ 20=  CH2/OH    H2C :  O+  H2O. 


4  ORGANIC  SYNTHESES. 

(6)  The  oxidation  and  removal  of  all  the  hydrogen  as  waterr 
and  the  simultaneous  oxidation  of  the  carbon  to  carbon  di- 
oxide: 

CH4+40  =  2H20+C02. 

From  the  above  considerations  it  may  be  seen  that  the 
oxidation  of  hydrocarbons  may  occur  along  the  following 
general  lines: 

(1)  Oxidation  by  removal  of  hydrogen  in  the  form  of  water. 

(2)  Oxidation  of  hydrogen  to  hydroxyl. 

(3)  Oxidation  of  carbon  to  carbonyl.1 

In  the  first  case,  oxygen  itself  does  not  enter  the  molecule. 
This  character  of  reaction  is  not  a  very  general  one,  and  when 
it  does  occur  is  usually  brought  about  in  an  indirect  manner. 
It  leads  to  the  formation  of  unsaturated  compounds  or  con- 
densation products. 

In  the  last  two  cases,  oxygen  enters  the  molecule,  but  there 
is  a  difference  in  its  mode  of  combination;  in  the  second  re- 
action only  one  valence  of  the  carbon  atom  is  held  by  oxygen, 
the  second  valence  of  the  latter  atom  being  attached  to  hydro- 
gen (the  hydroxyl  group,  alcohols)  or  to  another  similar  ele- 
ment or  group  (the  alcoholates,  —  ONa,  the  ethers,  —  O.CH3r 
etc.).  In  the  third  reaction,  both  the  valences  of  the  oxygen 
atom  are  directly  attached  to  the  carbon  to  form  the  carbonyl 
group,  =C:0  (the  aldehydes,  -HC:0,  the  ketones,  =C:0, 
and  the  acids,  -C:O.OH). 

Some  processes  of  oxidation  occur  with  much  more  readiness 
than  others;  for  instance,  the  direct  oxidation  of  a  hydrogen 
atom  in  a  hydrocarbon  nucleus  to  the  hydroxyl  group  is  rather 
rare,  and  will  only  take  place  under  certain  conditions : 

CH4  +  0->CH3.OH. 

A  group,  however,  already  containing  oxygen  is  more  susceptible 
of  oxidation  as  a  rule.     For  instance,  the  alcohol,  CH3OH,  is 

'See  also  A.  Wagner,  Action  of  Oxidants,  Warsaw,  1888  (Russian). 


OXIDATION.  5 

rather  easily  oxidized  to  the  aldehyde : 

CH3.OH  +  0-»H.CH:0. 

S  In  the  case  of  compounds  containing  several  hydrocarbon 
residues,  it  is  recognized  as  a  general  law  that  when  an  alcohol 
is  further  oxidized  the  second  oxygen  atom  becomes  attached  to 
the  carbon  atom  already  joined  to  the  hydroxyl  group.,  This 
causes  the  attachment  of  two  hydroxyl  groups  to  a  single  carbon 
atom,  which  is  a  very  unstable  grouping  and  immediately 
breaks  down  with  the  elimination  of  water  and  the  formatioa 
of  the  carbonyl  group: 

CH3  CH3 

I         +o  -» |   / 

CH2.OH  CH< 

\ 

CH3  CH3 

/QH  ->  |        +H20 

CH\OH        CH:0 

In  the  case  of  primary  alcohols  containing  the  group 
— CH2.OH,  further  oxidation  causes  the  formation  of  alde- 
hydes, having  the  group  — CH:0;  with  secondary  alcohols,  or 
those  containing  the  group  >CH.OH,  ketones  are  formed  with 
the  group  >C:O.  InAhe  case  of  tertiary  alcohols,  or  those 

containing  the  group  -^C.OH,  as  there  are  no  more  hydrogen 

atoms  capable  of  oxidation  to  hydroxyl,  the  molecule  is  broken 
down  with  the  formation  of  acids  having  a  less  number  of  carbon 
atoms.  As  the  aldehyde  group  still  contains  a  hydrogen  atom,, 
it  may  be  further  oxidized  with  the  formation  of  acids: 

-CH:0  +  0  ->  -CO.OH. 

Ketones,  on  the  other  hand,  cannot  be  further  oxidized;  if  the 
oxidant  employed  is  sufficiently  powerful,  the  ketone  is  broken 
up  into  compounds  having  a  less  number  of  carbon  atoms. 
In  order  to  show  the  various  possibilities  in  the  oxidation 


ORGANIC  SYNTHESES 


of  the  methyl  group,  or  its  derivatives,  the  following  list  of  the 
theoretical  product  of  propane  is  given : 1 


.  CH3 

CH2.OH 

(2) 

CH3. 

(3) 

CH2.OH 

CH2 

CH2 

CH.OH 

CH.OH 

1 

1 

1 

1 

CH3. 

CH3. 

CH3 

CH3 

Propane. 

Primary  propyl 
alcohol. 

Secondary  propyl 
alcohol. 

Propylidene 
glycol. 

(4) 

"   (5) 

(6) 

(7) 

CH2.OH 

i 

CH:0 

i 

CH3 

i 

CH2.OH 

i 

CH2 

CH2 

io 

CH.OH 

I 

1 

1 

I 

CH2.OH 

CH3 

CH3 

CH2.OH 

Propylene 

Propyl-aldehyde 

Acetone. 

Glycerol. 

glycol. 

(8)* 

(9)* 

(10) 

(11) 

CH:0 

i 

CH:0 

i 

CH2.OH 

i 

COOH. 

i 

CH2 

CH.OH 

CO 

CH2 

1 

1 

1 

1 

CH2.OH 

CH3 

CH3 

CH3 

Acetol. 

Propionic  acid. 

(12) 

CH2.OH 

(13)* 

CH2.OH 

(14)* 

CH:0 

(15)* 

CH3 

CH.OH 

io 

CH2 

CO 

1 

1 

1 

1 

CH.-O 

CH2.OH 

CH:0 

CH:0 

Glyceric  aldehyde. 

(16) 

CH2.OH 

(17) 

CH3 

(18)* 

CH:0 

(19)* 

CH:O 

CH2 

CH.OH 

CH.OH 

CO 

CO.OH 

CO.OH 

CH:0 

CH2.OH 

Ethylene 

Ethylidene 

lactic  acid. 

lactic  acid. 

1  Hjelt  (trans.  Tingle),  Principles  of  General  Organic  Chemistry,  p.  105. 


OXIDATION. 

(20)  (21)  (22)  (23)* 

CH:0  CH3  CH2.OH  CH:0 

I  I  I  I 

CH2  CO  CH.OH  CH.OH 

CO.OH  CO.OH  CO.OH  CO.OH 


Fonnyl  acetic  Pyroracemic  Glyceric 

acid.  acid.  acid. 


(24)* 

CH2.OH 

(25) 

CO.OH 

(26)* 

CH:0 

|o 

CH2 

i° 

CO.OH 

CO.OH 

CO.OH 

(27) 

CO.OH 


H.OH 


A 
i, 


OH 

Malonic  Oxymalonic 

acid.  acid. 


(28) 

CO.OH 


I0 

co.< 


.OH 

Mesoxalic  acid. 

The  compounds  whose  formulas  are  unnamed  and  marked 
Tvith  an  asterisk  have  not  yet  been  prepared. 

Aromatic  compounds,  or  those  containing  closed  rings  of 
carbon  atoms,  are  not  as  readily  oxidized  in  general  as  open- 
chain  compounds.  Oxidation  of  a  compound  containing  a  ben- 
zene ring,  together  with  a  side  chain,  usually  results  in  the  con- 
version of  the  latter  into  the  carbonyl  group;  and  it  makes  no 
difference  how  extensive  or  complicated  the  side-chain  may  be,1 


1  When  several  side-chains  are  present  in  aromatic  compounds,  their  rela- 
tive position  in  the  molecule  exerts  considerable  influence  on  the  direction 
and  extent  of  oxidation  For  instance,  dilute  nitric  acid  does  not  oxidize 
metaxylene,  C6H4(CH3)2,  whereas  it  oxidizes  paraxylene  to  paratoluic  acid, 

</^TT 
roVlH*     ^  *s  a^so  *°  ^e  observed  that  when  a  halogen  atom  is  present 

in  the  benzene  ring  in  the  ortho- position  to  a  methyl  group,  the  latter  does  not 
AS  readily  suffer  oxidation  with  acid  oxidants.     (Berickte,  vol.  24,  p.  3778). 


ORGANIC  SYNTHESES. 

it  will  nearly  always  break  down  to  the  simple  carbonyl  grou  & 
C6H5.CH3  -»  C6H5.CO.OH, 

->  C6H5.CO.OH. 


The  reaction  may  sometimes  be  controlled  by  the  use  of 
mild  oxidizing  agents,  as,  for  instance,  in  the  oxidation  of 
cymene  : 

CH3  — 


e         prr  3  —      o.4\  fYrvm 

L  \CH3  \CH 

and    CeH,    and 


,  PTT.  ,  .OH 

and    C6H  and 


TT/CO. 

S 


\CH3 
II.  ACTION  OF  OXIDIZING  AGENTS. 

Oxidation  may  be  brought  about  either  directly  by  the 
action  of  a  suitable  oxidizing  agent  (as  in  the  oxidation  of 
anthracene  to  anthraquinone  by  the  action  of  chromic  acid) 
or  indirectly  through  the  formation  of  intermediate  compounds 
(as  in  the  preparation  of  phenol  from  benzene  by  first  sulpho- 
nating  the  latter  by  treatment  with  sulphuric  acid,  and  then 
fusing  the  sulphonic  acid  so  obtained  with  caustic  potash)  :  1 

1  Lassar-Cohn  makes  the  following  remarks  in  regard  to  the  carrying  out  of 
oxidations  in  organic  chemistry:  (a)  When  the  product  of  oxidation  is  readily 
decomposed  by  the  further  action  of  the  oxidant,  it  is  frequently  possible  to 
add  to  the  solution  a  carefully  chosen  extracting  solvent,  so  that  on  the  addi- 
tion of  the  oxidant  the  whole  may  be  shaken  and  the  product  removed  from 
the  influence  of  the  latter  by  the  solvent.  The  use  of  ice  for  the  purpose  of  main- 
taining a  low  temperature  also  has  a  beneficial  effect  at  times,  (b)  If  the  product 
of  oxidation  is  volatile  in  steam,  a  current  of  the  latter  may  be  conducted  through 
the  solution  during  the  oxidation,  (c)  In  many  cases  where  the  preparation 
of  a  particular  oxidized  product  is  especially  difficult,  it  is  frequently  possible 
to  judiciously  choose  some  derivative  of  the  substance  to  be  operated  on,  which 
by  proper  treatment  will  yield  the  same  product.  —  Manual  of  Organic  Chemistry 
(trans.  Smith),  p.  244. 


OXIDATION. 


OTT  PO 

(a)3C6H4</|    \CeH4 +  2Cr03  =  3C6H4/ 

XCH/  XCO 


+3H20+Cr203. 

(b)  C6H6-fH2S04=C6H5.S02.OH 

C6H5.S02.OH  +  KOH  =  C6H5.OH  +  KHS03. 

Oxidation  may  also  occur  in  two  different  directions:  (ajs 
The  compound  may  contain  the  same  number  of  carbon  atoms^ 
after  oxidation  as  before  : 

CH3.CH2OH  +  0  =  CH3.CH  :  0  +  H2(X 

Alcohol.  Aldehyde. 

(b)  The  oxidation  may  be  accompanied  by  a  decomposition 
of  the  molecule,  with  the  formation  of  two  or  more  substances 
containing  fewer  carbon  atoms  than  the  original  compound: 

CH3.CO.CH3  +  20,.  =  CH3.CO.OH  +  C02  +  H20. 

Acetone.  Acetic  acid.'  Carbon  dioxide. 

This  latter  form  of  oxidation  is  especially  liable  to  occur  witla 
the  unsaturated  compounds  of  the  aliphatic  series,  as  in  the 
oxidation  of  crotonic  acid  to  a  mixture  of  acetic  and  oxalic 
acids, 

COOH 
CH3.CH  :  CH.CO.OH  +  202  =  CH3.CO.OH  +  1 

Crotonic  acid.  Acetic  acid.  COOH 

Oxalic  acid.- 

or  of  allyl  alcohol  to  formic  and  oxalic  acids  : 

CO.OH 
CH2  :  CH.CH2.OH  +  302  =  H.CO.OH  +  1 

Allyl  alcohol.  Formic  acid.       QQ  QJJ 

Oxalic  acid. 

In  such  cases  the  compound,  as  a  rule,  breaks  down  at  the 
position  of  the  double  bond. 

In  some  reactions,  oxidation  may  result  in  the  condensation! 
of  the  compound,  either  in  its  own  molecule  or  with  other  sub- 
stances, by  reason  of  the  elimination  of  hydrogen  by  the  oxygeiu. 


10  ORGANIC  SYNTHESES. 

For  instance,  the  oxidation  of  dibenzyl  leads  to  the  formation  of 
toluylene : 


C6H5-CH2          C6HS-CH 

+0=  || 

Hr<  TT       r»TT 
2  L/6A15 L/Jtl 

Dibenzyl.  Toluylene 


)-"--*-{J  VXJ 

aJ] 

jii* — (J 


The  formation  of  pararosanihne  by  the  oxidation  of  a  mixture 
of  aniline  and  paratoluidine  is  also  an  illustration  of  this  re- 
action: 

]H"™HjC6H4.NH2 
~:jlT"HiC6H4.NHiHl 


A  large  number  of  different  bodies  may  be  employed  as 
oxidants,  though  the  action  of  different  oxidants  may  vary 
considerably  towards  the  same  organic  compound.  The  oxi- 
dation of  aniline  by  various  oxidants  may  be  taken  as  an  illus- 
tration. When  treated  with  a  mixture  of  manganese  dioxide 
and  sulphuric  acid,  aniline  yields  ammonia  and  a  small  amount 
of  quinone.1  When  oxidized  with  chromic  acid  mixture,  how- 
ever, a  quantitative  yield  of  quinone  is  obtained;  with  an  al- 
kaline solution  of  potassium  permanganate,  aniline  is  con- 
verted into  azo-benzene,  ammonia,  and  oxalic  acid;2  whereas, 
in  an  acid  solution,  the  same  oxidant  gives  aniline  black,  and,  in 
a  neutral  solution,  nitre-benzene  and  azo-benzene  are  formed;  3 
boiled  with  a  solution  of  bleaching-powder,4  aniline  gives  nitro- 
benzene; with  an  acid  solution  of  hydrogen  peroxide,  ammonia 


*  C6H6.NH2+02=C6H40+NH3. 

>  3C6Hs.NH.+  50=C6H6N:N.C6Ha+  NH3+  (COOH)2+H2O. 
»  3C6H6.NH2+  30=  C6H5.N :  N.C6H,+  C6H5.NO2+  3H2O. 

4  Ortho-nitrobenzal-acetone  is  converted  into  ortho-nitro-cinnamic  acid   by 
the  oxidizing  action  of  sodium  hypochlorite  (mixture  of  bleaching-powder  and 


OXIDATION.  II 

and  dianilido-benzoquinone-anilide  is  formed;  while,  in  a  strong 
acid  solution,  the  same  oxidant  gives  an  induline  derivative.1 

The  following  summary  gives  the  principal  oxidizing  agents 
employed,  together  with  a  brief  account  of  their  action:2 

Oxygen  acts  directly  only  on  easily  oxidizable  substances. 
Air,  when  acting  in  the  presence  of  heated  platinum  or  platinum 
sponge,  will  oxidize  primary  alcohols  to  aldehydes,  and  even 
aldehydes  themselves  are  gradually  converted  into  acids. 
Formaldehyde,  for  instance,  may  be  prepared  by  conducting  a 
mixture  of  methyl  alcohol  vapor  and  air  over  a  heated  platinum 
spiral.  The  hydrochloride  of  paraphenylene-diamine  is  easily 
oxidized  by  exposure  to  the  air,  giving  almost  a  theoretical 
yield  of  tetra-amido-diphenyl-para-azophenylene  : 

N:C6H3.NH2 


By  passing  the  vapors  of  many  'substances  mixed  with  air 
over  a  heated  spiral  of  copper  superficially  oxidized,  oxida- 
tion products  are  obtained,  as  a  rule,  more  readily  than  with 
a  platinum  spiral.  Ethyl  ether,  for  instance,  is  oxidized  to 
aldehyde, 

CH3.CH2  \r\        CHg.CHO  ,  TT  r\. 

CH3.CH2/U     *  CH3.CHO  + 

and  toluene  gives  benzaldehyde  : 

C6H5.CH3  ->  C6H5.CHO.+H20. 

sodium  carbonate): 


1  Benzylidene-acetone  is  converted  into  cinnamic  acid  by  the  oxidizing  action 
of  bromine  in  alkaline  solution.     The  oxidizing  action  of  bromine  has  also  been 
made  use  of  among  the  carbohydrates;    for  instance,  by  heating  nsrtk-sugar  with 
bromine  an  acid  is  formed;    by  heating    glycerol  with  bromine  and  soda-ash, 
glycerose  is  formed. 

2  For  a  detailed  discussion  of  the  different  oxidizing  agents  employed  in 
organic  syntheses,  see  Lassar-Cohn,  Manual  of  Organic  Chemistry,  pp.  243-286. 


12  ORGANIC  SYNTHESES. 

Silver  oxide  in  alkaline  solution  readily  oxidizes  aldehydes 
to  acids,  with  the  precipitation  of  metallic  silver : 

2CH3.CHO  +  3Ag20 = 2CH3.COO.Ag  +  H20  -f  2Ag2. 

Glycerol  is  converted  into  gly collie  acid.  The  ammoniacal 
solution  of  silver  oxide  for  the  testing  of  aldehydes  is  best  pre- 
pared by  mixing  a  solution  of  10  parts  silver  nitrate  in  100 
parts  water  with  one  of  10  parts  caustic  soda  in  100  parts  water, 
:and  then  adding  ammonia-water  drop  by  drop  until  the  pre- 
cipitate of  silver  oxide  has  completely  dissolved.  The  solution 
should  be  kept  in  a  dark  place. 

Manganese  dioxide  is  used  in  connection  with  sulphuric  acid 
'for  oxidation  in  acid  solutions.  When  the  vapor  of  alcohol  is 
conducted  over  pyrolusite  heated  to  150-360°  Cv  it  is  mostly 
^converted  into  acetone. 

Potassium  permanganate  is  perhaps  more  frequently  used 
than  any  other  oxidizing  agent.  It  may  be  employed  in  neutral, 
.acid,  or  alkaline  solution.1  In  neutral  solution  it  acts  as  follows : 

2KMn04  +xH20=  2Mn02.xH20+2KOH  +  30. 

In  alkaline  solution  the  reaction  is  the  same.  In  acid  solution 
It  is  as  follows : 

2KMn04 + 3H2S04  =  2MnS04 + K2S04  +  3H20  4-  50. 

Compounds  containing  hydrogen,  linked  to  a  tertiary  carbon 
atom,  have  the  hydrogen  converted  into  hydroxyl  by  the  action 
of  an  alkaline  solution  of  potassium  permanganate : 

T)  T? 

R-^CH  -»  R^C-OH. 

^ R/  R/ _ 

1  Reichardt,  in  his  investigations  on  the  action  of  different  oxidizing  agents 
•on  soluble  starch,  found  that  potassium  permanganate  in  acid,  alkaline,  and 
neutral  solutions,  and  chromic  acid,  have  an  energetic  action,  but  all  give  rise 
to  indefinite,  dirty-brown  products;  chlorine  and  alkaline  copper  hydrate  solu- 
tion gave  the  same  result;  but  by  warming  the  starch  solution  with  bromine 
and  afterwards  treating  the  product  with  silver  oxide,  gluconic  acid  was  obtained. 
Starch  heated  with  nitric  acid  gave  carbon  dioxide  and  oxalic  acid,  whereas 
.fuming  nitric  acid  gave  a  mono-nitro-derivative. 


OXIDATION.  13 

The  group  =CH2  is  usually  converted  into  CO  by  the  action  of 
potassium  permanganate. 

Chromic  acid  is  extensively  used  for  the  preparation  of  alde- 
hydes, ke tones,  and  acids  from  alcohols;  for  the  oxidation  of 
aromatic  hydrocarbons  (with  the  exception  of  the  ortho-com- 
pounds), and  for  'the  preparation  of  quinones.  Chromic  acid 
is  almost  always  used  in  acetic  acid  solution,  as,  when  dissolved 
in  water,  it  gives  a  precipitate  of  chromic  oxide.1  A  mixture 
of  potassium  bichromate  and  sulphuric  acid  may  also  be  used; 
this  is  known  as  "chromic  acid  mixture."  For  the  oxidation 
of  the  aromatic  hydrocarbons,  a  mixture  of  4  parts  K2Cr207 
and  6  parts  H2S04,  diluted  with  twice  its  volume  of  water,  is 
found  to  be  most  suitable.  In  the  case  of  alcohols  a  more 
dilute  solution  is  necessary.  Many  compounds,  such  as  oxy- 
acids,  ketones,  etc.,  may  be  decomposed  by  chromic  acid  mix- 
ture, with  the  formation  of  products  containing  less  carbon 
atoms.  A  mixture  of  potassium  bichromate  and  acetic  acid  is 
sometimes  used;  other  acids  may  also  be  substituted.  The 
oxidizing  power  of  these  mixtures  is  calculated  on  the  principle 
that  the  Cr03  is  converted  into  Cr203 : 

K2Cr207 + 4H2S04  =  K2S04  +  Cr2(S04)3 + 4H20 + 30. 

i  • ; 

Chromyl  chloride  is  another  useful  oxidizing'  agent,  es- 
pecially for  converting  the  methyl  groups  in  aromatic  hydro- 
carbons into  aldehyde  groups.  Thus,  nitro toluene  is  con- 
verted into  nitrobenz aldehyde.  Chromyl  chloride  is  prepared 
by  acting  on  a  mixture  of  salt  and  potassium  bichromate  with 
fuming  sulphuric  acid : 

K2Cr  207 + 4NaCl  +  3H2S207  = 

2Cf  02C12 + K2S04 + 2Na2S04  +  3H2S04. 

* - 

1  The  formation  of  the  oxide  may  sometimes  interfere  with  the  proper  course 
of  the  reaction,  especially  in  the  case  of  organic  acids,  where  the  latter  may  com- 
bine with  the  oxide.  Should  the  solution  of  chromic  acid  in  water  be  used,  it 
is  best  to  acidify  it  with  sulphuric  or  hydrochloric  acid.  The  use  of  an  acetic 
acid  solution,  however,  is  further  favored  by  the  fact  that  many  of  the  bodies 
which  it  is  the  purpose  to  oxidize  may  be  dissolved  therein,  and  the  speed  of 
oxidation  then  regulated  by  gradual  addition  of  chromic  acid. 


14  ORGANIC  SYNTHESES. 

The  action  of  chromyl  chloride  is  very  violent,  and  it  must  be 
used  in  carbon  disulphide  solution.  It  is  probable  that  at  first 
double  compounds  are  formed  between  the  hydrocarbons  and 
the  chromyl  chloride,  which  are  decomposed  by  water  with  the 
formation  of  aldehydes : 

3C6H5.CH3(Cr02Cl2)2  =  3C6H5.CHO +2Cr2Cl6  +  2Cr03 +3H20. 

Nitric  acid  may  be  used  as  an  oxidant,  though  it  also  has  a 
nitrating  action.  When  employed  as  an  oxidant,  nitric  acid 
diluted  with  two  molecules  of  water  is  generally  used;  such  an 
acid  acts  less  energetically  than  chromic  acid  mixture.  Con- 
centrated nitric  acid  usually  converts  compounds  of  the 
methane  series  into  oxalic  acid  or  carbon  dioxide. 

Caustic  potash  acts  as  an  oxidant  when  it  is  fused  with  the 
substance.  The  higher  primary  alcohols  in  this  manner  yield 
acids.  Phenols,  when  fused  at  high  temperatures  with  caustic 
potash,  give  diphenols.1  Unsaturated  compounds  are  usually 
decomposed  by  fusion  with  caustic  potash,  the  carbon  chain 
being  broken  at  the  position  of  the  double  bond,  the  products 
being  oxidized  to  acids.  Hydrosorbic  acid,  for  instance,  gives 
acetic  and  butyric  acids : 

CH3.CH :  CH.CH2.CH2.CO.OH  +  2KOH 

Hydrosorbic  acid.  =  CH3.COOK  +  C3H7.COOK  +  H2. 

1  Oxidation  produced  through  fusion  with  caustic  potash  is  a  peculiar  one. 
Prima  y  alcohols  are  converted  directly  into  acids: 

C^Hgg.  OH+  KOH=  C16H33O.OK+  2H, 
Cetyl  alcohol.  Palmitic  acid. 

Phenols  are  also  oxidized  by  the  same  means  at  high  temperatures,  the  reac- 
tion varying  with  the  composition  of  the  phenol,  hydrogen  being  evolved  in 
each  case.  Phenol,  for  example,  gives  diphenol: 

2C6H5.OH+  2KOH=  KO.C6H4.C6H4.OK+  H2+  2H2O. 
Resorcinol  gives  diresorcinol  and  some  phloroglucinol: 

C6H4.  (OH)2+  3KOH=  C6H3(OK)>  2H2O+  H^ 
With  cresol,  the  side-chain  is  oxidized: 

C«H\CH3+2KOH=C^\COOK+3H2.  • 


OXIDATION.  15 

III.   DIRECT  OXIDATION. 

A.  Oxidations  which  Preserve  the   Same  Number  of 
{Jarbon  Atoms  in   the   Molecule. 

Attention  has  already  been  drawn  to  the  fact  that  oxida- 
tion may  be  either  direct  or  indirect,  and  that  the  former  mode 
may  in  turn  be  subdivided  into  (1)  oxidation  which  preserves 
the  same  number  of  carbon  atoms  in  the  molecule,  and  (2) 
oxidation  accompanied  by  a  greater  or  less  destruction  or 
breaking-down  of  the  molecule.  When  the  destruction  of  the 
body  is  complete,  with  the  formation  of  carbonic  acid,  the 
oxidation  is  termed  combustion. 

The  various  radicals  or  groups  to  be  met  with  in  organic 
chemistry  will  now  be  examined  with  reference  to  their  be- 
havior with  oxidants. 

The  -CH3  group  is  oxidized  almost  exclusively  only  in 
aromatic  compounds.  It  is  then  changed  into  the  aldehyde 
group,  -CHO,  or  the  carboxyl  or  acid  group,  -CO. OH.  It  is 
difficult  to  cite  any  examples  in  the  paraffin  series  of  the  oxi- 
dation of  the  -CH3  group  into  -CHO  or  -CO.OH;  about  the 
only  cases  known  are  the  conversion  of  butyric  acid  into  suc- 
cinic  acid,  and  the  production  of  glyoxal  by  the  oxidation  of 
aldehyde : 

CH2.CH3       ~     CH2.CO.OH        CH3.,      CHO 


CH2.CO.OH         CHa.CO.OH        CHO        CHO 

Butyric  acid.  Succinic  acid.  Aldehyde.        Glyoxal. 

The  CH3  group  is  converted  into  CHO 1  by  decomposing  with 
water  the  double  compounds  of  the  aromatic  hydrocarbons  with 
chromyl  chloride.  The  compound  with  toluene,  for  example, 
should  apparently  be  represented  by  the  following  formula: 

'O.CrCl2.OH 


1  The  oxidation  of  the  CH3  group  into  CHO  may  be  effected  by  employing 
air  in  the  presence  of  an  oxidized  copper  spiral  (Low,  Jour.  pr.  Chem.,  vol.  91 
p,  323).     By  this    means    toluene,  C6H6.CH3,  is    converted  into   benzaldehyde, 
C6H6.CHO.     (See  above.) 


16  ORGANIC  SYNTHESES. 

The  decomposition  with  water  evidently  proceeds  in  accordance 
with  the  following  equation: 


+  3H20 
=  3C6H5.CHO  +  2Cr2Cl6  +  2Cr03  +  6H20. 

The  operation  is  carried  out  in  the  following  manner  :  1 

Dissolve  1  part  (1  mol.)  of  the  hydrocarbon  in  7  parts  of 
carbon  disulphide,  and  gradually  add,  with  cooling,  10-15  parts 
of  a  solution  of  1  part  (2  mols.)  of  chromyl  chloride  in  7  parts 
of  carbon  disulphide;  after  each  addition  wait  until  the  red 
coloration  has  disappeared.  The  precipitate  is  collected  on 
some  glass  wool,  washed  with  carbon  disulphide,  and  dried  on 
a  water-bath.  It  is  then  decomposed  by  gradually  pouring  into 
cold  water,  and  the  aldehyde  is  removed  by  means  of  ether. 
The  aldehyde  may  also  be  isolated  by  treating  the  solution  with 
a  current  of  sulphur  dioxide  gas.  Chromyl  chloride,  acting  on 
aromatic  hydrocarbons  with  side-chains,  transforms  them  into 
aldehydes;  with  benzene,  however,  quinone  is  formed. 

By  the  aid  of  chromyl  chloride,  not  only  can  the  CH3  group 
in  hydrocarbons  be  transformed  into  CHO,  but  also  in  their 
derivatives.  For  instance,  the  compound  propylphenyl-ketone, 
C6H5.CO.CH2.CH2.CH3,  when  oxidized,  gives  benzoyl-propylic 
aldehyde,  C6H5.CO.CH2.CH2.CHO.  2 

The  CH3  group  in  aromatic  compounds  is  converted  into 
CO.OH  by  the  action  of  most  oxidants.  In  this  manner  the 
hydrocarbons  are  transformed  into  organic  acids  either  by  dilute 

1  Chromyl  chloride  is  prepared  in  the  following  manner:     Fuming  sulphuric 
.acid  is  added  to  a  mixture  of  common  salt  and  potassium  bichromate  in  the  pro- 
portions indicated  by  the  following  equation: 

K2Cr207+  4NaCl+  SH^O,  =  2CrO2Cl2+  ig3O4+  2Na2SO4+  SH^O,. 

The  mixture  is  distilled  from  a  large  flask  until  the  contents  begin  to  foam. 
A  secondary  reaction,  resulting  in  the  liberation  of  chlorine,  proceeds  according 
to  the  following  equation: 

6CrO,Cl2+  SHj&Or-  2Cr2(SO4)3+  2Cr03+  6C12+  3H20. 

2  Burcker,  Ann.  de  Chem.  et  de  Phys.,  vol.  26,  p.  470. 


OXIDATION.  17 

nitric  acid,  chromic  acid  mixture,1  potassium  permanganate,  or 
even  by  fusion  with  caustic  potash.  The  fusion  with  caustic 
potash  is  principally  employed  for  the  purpose  of  oxidizing  the 
CH3  group  in  phenols.  This  fusion  should  be  carried  out  at  a 
temperature  of  200-250°  C.  for  several  hours;  4  to  5  parts  of 
caustic  potash  (KOH),  moistened  with  a  little  water,  are  used 
for  1  part  of  phenol.  The  end  of  the  reaction  is  indicated  by 
the  liberation  of  hydrogen  ceasing. 

In  the  case  of  amido  derivatives,  the  NH2  group  should  be 
preserved  against  the  action  of  oxidants  by  the  introduction  of 
an  acid  radical;  otherwise  there  would  result  quinones  and  azo- 
compounds.  Thus,  ^ 

r  R  /(I)  CH3 
°6±l4\(4)  NH.CO.CHs 

Acetyl-paratoluidine. 

gives,  on  oxidation, 

coo* 

rH/(l)CO.OH 
UM4\(4)  NH.CO.CHs* 

Acetyl-paramido-benzoic  acid. 

The  presence  of  the  N02  group  often  protects  the  NH2  group 
from  oxidation:  thus,  dinitrotoluidine,  on  oxidation  with 
chromic  acid  mixture,  gives  amido-dinitro-benzoic  acid  : 

CH3  COOH 


NH2  NH2 


Frequently  different  oxidants  do  not  behave  in  the  same 

//-i  \    p~CT 

manner.    Thus  orthotoluic  acid,  C6H4<^  L)  COOH'  ^ves  phtha- 

lic  acid  when  oxidized  by  potassium  permanganate;   but  when 
treated  with  chromic  acid  mixture  it  is  completely  decomposed 

1  In  place  of  chromic  acid  mixture  (4  parts  potassium  bichromate  and  5  parts 
sulphuric  acid)  there  may  be  employed  a  solution  of  chromic  acid  in  glacial  acetic 
•acid. 


1 8  ORGANIC  SYNTHESES. 

/ '/1\ 

into  carbonic  acid.    In  the  same  way  cymene,  C6H4\  ,*(  n  -r    > 

\W  ^3*17 

by  the  oxygen  of  the  ah-  (as  in  the  animal  organism),  is  trans- 
formed into  cuminic  acid,  C6H4^  m  £  jj  >  by  the  oxidation  of 

the  CH3  group  and  transformation  of  the  C3H7  group  into  its 
isomeric  form;  but  when  oxidized  with  dilute  nitric  acid,  it  is  the 
C3H7  group  which  is  attacked,  and  paratoluic  acid  is  produced, 

l  poOH'  w^ch  on  father  oxidation  yields  terephthalic 

acid,  C6H4<^  ^J,  COOH'  ^ien  ^ne  aromatic  hydrocarbon  con- 
tains groups  other  than  CH3  and  of  the  formula  CnH2n+i,  they 
are  oxidized  like  CH3  and  are  all  transformed  into  COOH.  Thusr 
ethyl-benzene,  C6H5.CH2.CH3,  on  oxidation  gives  benzoic  acid, 
CeHs.COOH.  If,  besides  these  groups,  the  hydrocarbon  con- 
tains another  side-chain  of  CH3,  the  latter  is  oxidized  subse- 
quently, as  in  the  case  of  the  oxidation  of  cymene  to  paratoluic 
acid,  and  then  to  terephthalic  acid. 

The  presence  of  the  acid  groups,  N02,  COOH,  S02OH,  ren- 
ders the  oxidation  more  difficult.  Thus,  while  toluene,  C6H5CH3,. 

/Cl 
and  its  mono-chlor  derivative,  CeH4<^  ^ -^  ,  are  easily  oxidized  by 

the  action  of  dilute  nitric  acid,  nitro-toluene,  CeH^  pjr2>  is  only 

oxidized  by  chromic  acid  mixture,  or  by  heating  with  dilute  nitric- 
acid  in  a  sealed  tube;  and  the  corresponding  dinitro-derivative,. 

C6H*\  n-cj       j  is  not  oxidized  by  even  chromic  acid  mixture. 
^\uti3 

If  the  CH3  is  in  the  ortho  (1:2)  position  with  an  acid  group,, 
it  cannot  be  oxidized  by  either  nitric  acid  or  chromic  acid 
mixture;  it  is  necessary  to  use  potassium  permanganate  in  al- 
kaline solution,  or  fusion  with  potash. 

Furthermore,  it  should  be  noted  that  in  the  oxidation  of 
unsymmetrical  pseudocumene,  C6H3(CH3)3(l-2:4),  by  dilute 

nitric  acid,  there  are  formed  two  isomeric  acids,  C6H3^  /nTJ  N  r 

Xw-ti3j2 


OXIDATION.  19 

xylilic  and  paraxylilic  acids,  according  to  which  CH3  is  oxidized; 
but  in  the  oxidation  of  the  symmetrical  hydrocarbon,  mesity- 
lene,  C6H3(CH3)3 (1:3:5),  there  is  only  one  acid  obtained, 

<POOTT 
(OH  ")  J  as  may  ^e  rea^y  understood. 

The  CH2  group  in  aromatic  compounds  is  oxidized  and  con- 
certed into  the  carbonyl  group,  CO,  by  means  of  chromic  acid 
mixture,  solution  of  chromic  acid  in  acetic  acid,  or  dilute  nitric 
acid.  In  this  manner  the  ketones  are  obtained : 

/C6H5 

\      p     TT » 

\U6-tl5 
Diphenylmethane.  Benzophenone. 

The  CH2  group  undergoes  oxidation  even  in  preference  to 
the  CH3  group.  Thus,  by  the  action  of  a  solution  of  chromic 
acid  in  acetic  acid,  ethylbenzene  gives,  simultaneously  with 
tenzoic  acid,  the  ketone  C6H5.CO.CH3. 

The  CH  group  is  characterized  by  the  ease  with  which  it 
is  converted  into  the  tertiary  alcohol  group,  C.OH,  which  is 
true  not  only  in  aromatic  compounds,  but  also  in  the  paraffins. 
Thus,  isobutyric  acid,  CH(CH3)2.COOH;'  by  the  action  of  an 
alkaline  solution  of  potassium  permanganate  is  converted  into 
oxy-isobutyric  acid,  C(OH)(CH3)2.COOH.  Cuminic  acid  be- 
haves in  the  same  manner,  being  converted  into  oxycuminic 
acid.  When  the  CH  is  in  the  ^-position  to  a  carboxyl  group, 
instead  of  obtaining  an  hydroxy-acid  on  oxidation,  a  ketone  is 
formed  by  the  splitting-off  of  water. 

(CH3)2.CH. 

CH2 

gives,  on  oxidation, 
CH2 

COOH 
By  the  same  method  of  oxidation  as  above,  the  compound 


ORGANIC  SYNTHESES. 

ITT  pTT 

6302OH     gives  C6H3^S02OH  ;  but  if  dilute  ni- 

\CH(CH3)2  \C.(OH)(CH3)2 

/CH3 

trie  acid  is  used  as  the  oxidant,  there  is  formed  CeHsr—  S02OH 

XCOOH 

instead.  Triphenylmethane,  CH(C6H5)3,  is  converted  into 
triphenylcarbinol,  C.OH(C6H5)3,  by  the  action  of  chromic  acid^ 
The  CH  group,  which  forms  a  part  of  the  closed  benzene 
ring,  on  the  contrary  is  oxidized  with  difficulty,  and  in  the 
majority  of  cases  only  by  indirect  means.  Benzene  is  con- 
verted  into  phenol  by  oxygenated  water,  or  by  oxygen  in  the 
presence  of  aluminium  chloride;  in  the  presence  of  sulphuric 
acid,  benzene  gives  quinone  by  the  action  of  oxygenated  water. 
The  presence  of  OH  in  benzene  renders  the  CH  more  sus- 
ceptible to  oxidation;  phenol,  CeH5.OH,  on  fusion  with  soda 
in  the  air,  gives  pyrocatechol,  and  resorcin  yields  phloroglucol  ; 
polyhydric  phenols  in  alkaline  solution  combine  energetically 
with  the  atmospheric  oxygen,  giving,  among  other  products, 
acetic  acid  and  carbon  dioxide. 

CH          CO 

The  conversion  of  the  group  |      into   |      in  the  compounds 

CH          CO 


of    the    type    R"<   |      >R"    and    ||     >R",    as    anthracene, 

CH/ 

x  CH  —  CG^ 

;>CeH4  and  phenanthrene  1  1  can  be  explained 

/  CH—  C6H4 

by  admitting  the  formation  of  2(C.OH),  which  fixes  0  +  H2Or 
and  then  splits  off  water,  2H20.    Thus,  with  anthracene  there 

OlHl 


/\  iOH!\ 
is  first  formed,  C6H4<T      ^iXTrOCeHi,  then  2H20  is  eliminated. 


It  is  doubtless  by  the  aid  of  an  analogous  reaction  that 
terebenthene,  Ci0Hi6,  is  transformed  into  camphor,  CioHi6Or 


OXIDATION.  2* 

and  the  latter  is  itself  transformed  into  camphoric  acid,  which 
would  not  be  formed  by  the  simple  fixation  of  oxygen.  For  it 
has  been  shown  by  Friedel l  that  camphoric  acid  is  not  a  dibasic 
acid,  but  a  compound  of  alcohol,  ketone,  and  acid,  as  is  indi- 
cated by  the  formula: 

COOH 


J.OH 
CH2/\CO 


\/ 


CH2\/CH2 
CH 

C3H7 

The  CH.OH  group  is  easily  oxidized  to  CO*  by  nitric  acidr 
chromic  acid,  potassium  permanganate,  or  chromic  acid  mix- 
ture. In  these  reactions  there  are  frequently  obtained  secondary 
products  arising  from  the  decomposition  of  the  compounds  at 
first  formed.  In  this  manner,  secondary  alcohols  are  con- 
verted into  ke tones  by  the  action  of  oxidants;  lactic  acid,  by 
reason  of  its  CH.OH  group,  gives  pyruvic  acid  with  potassium 
permanganate : 

CH3      \riTT  nTT       ——^       CH3      \p/~k 

r*r\f\~tt  /V-'JJL.V/.Q.  r<r\r\Tj  /vA/. 

L/UU-tl/  UUUJuL/ 

The  CHOH  group  in  certain  cases  is  oxidized  even  more 
readily  than  the  CH2.OH  of  primary  alcohols;  the  oxidation 

C6H5.CH.OH 

of     phenyl-glycol,  ,  gives     the     ketone-glycol 

CH2.OH 
C6H5.CO 

,  together  with  a  small  quantity  of  ketonic  acid,. 
)H2OH 

1  Bull.  Soc.  Chim.,  1889,  p.  83. 

2  This  reaction  may  be  considered  as  taking  place  in  the  following  manner ; 

=  C=O. 


22  ORGANIC  SYNTHESES. 

C6H5.CO       .    In  the  case  of  saturated   polyhydric  alcohols, 

COOH 

the  contrary  is  true,  and  the  CH2OH  is  oxidized;  in  this  manner 
aldehydic  acids  may  be  prepared.  Thus,  erythrite  yields 
erythric  acid: 

C4H605     —  ->     OCH.CHOH.CHOH.COOH. 

The  CH2OH  group  on  oxidation  is  changed  into  CO. OH  or 
CHO.1  It  is  converted  into  CO.OH  by  the  action  of  numerous 
oxidants,  and,  in  certain  cases,  by  the  action  of  atmospheric 
oxygen  in  the  presence  of  platinum  .black.2  It  was  in  this 
manner  that  Grimaux3  prepared  the  first  synthetic  sugar  by 
oxidizing  glycerol.  Primary  alcohols  by  this  means  can  be 
converted  into  acids.  The  action  of  the  platinum  black  is  at 
times  too  energetic,  and  the  reaction  must  be  moderated  by 
diluting  the  alcohol  with  water.  If  the  alcohol  is  very  volatile, 

1  The  mechanism  of  these  reactions  is  as  follows: 


-CH|H|0|H|+  |O|=  -CHO+H2O 


the  alcohol  group  may  also  be  considered  in  some  cases  as  being  directly  oxidized 
to  the  acid,  as  follows: 


-  C|HH|.OH+|0|b=  - 

This  is  a  very  probable  assumption,  because  the  H  in  the  hydroxyl  group 
of  the  alcohol  is  already  oxidized,  and  when  the  acid  is  formed  directly  it  is  more 
likely  that  the  two  H's  of  the  nucleus  are  oxidized  and  removed,  rather  than  one  H 
from  the  nucleus  and  one  from  the  hydroxyl  group.  In  fact,  the  first  oxida- 
tion of  the  alcohol  group  to  the  aldehyde  may  be  more  logically  considered  as: 


-CH.HOH+  0=  -CH  -  H2O=  -CHO. 

2  The  CH2OH  group  may  be  oxidized  to  the  CHO  group  by  means  of  air  in 
the  presence  of  platinum.       (Hofmann,  Ann.,  vol.,  145,  p.  358;    Tollens,  Ber., 
vol.  19,  p.  2133.)    This  was  the  first  method  employed  for  the  preparation  of 
formaldehyde,  H.CHO,  from    methyl    alcohol,  CH3.OH.     Superficially  oxidized 
copper  has  been  found  to  be  even  more  effective  than  platinum.    (Low,  Jour.  pr. 
Chem.,  vol.  141,  p.  323.) 

3  Bull.  Soc.  Chim.,  vol.  45,  p.  481. 


OXIDATION.  23 

place  it  in  a  beaker  beside  another  one  containing  the  platinum 
black,  and  cover  the  whole  with  a  watch-glass. 

The  CH2OH  group  is  converted  into  CHO  usually  by  means 
of  chromic  acid  mixture,  this  being  the  customary  method  of 
preparing  aldehydes.  It  is  necessary  to  take  a  slightly  less 
quantity  of  alcohol  than  the  theoretical  amount.1  As  secondary 
products,  there  are  obtained  acetals  and  ethers  by  reason  of  a 
more  advanced  oxidation  giving  rise  to  some  acid  which  reacts 
on  the  alcohol.  The  aromatic  aldehydes  are  often  obtained  in 
a  different  manner.  The  chloride  corresponding  to  the  alcohol 
does  not  yield  the  latter  very  readily,  but  it  may  be  directly 
transformed  into  the  aldehyde  by  heating  with  a  nitrate,  and 
lead  nitrate  in  particular.  It  may  be  that  the  nitric  ether, 
which  is  at  first  formed,  is  saponified  by  the  water,  and  the 
nitric  acid  thus  liberated  oxidizes  the  alcohol  into  the  aldehyde. 
In  order  to  obtain  aldehydes  by  the  decomposition  of  ordinary 
ethers,  see  p.  55;  and  for  the  action  of  quinone  on  alcohol,  see 
p.  54. 

The  CHO  group  of  aldehydes  is  oxidized  to  CO. OH  by  the 
action  of  chromic  acid  mixture,  alkaline  solution  of  potassium 
permanganate,  etc.,  or  by  gradually  adding  to  the  solution  of 
the  aldehyde  in  glacial  acetic  acid  the  theoretical  amount  of 
chromic  acid  dissolved  in  the  same  solvent.  The  unsaturated 
aldehydes  are  easily  oxidized  by  the  action  of  silver  oxide. 

Aldehydes  are  also  oxidized  directly  by  atmospheric  oxygen : 

1  The    CH2OH    group    in   choline,    CH2.OH,    however,    gives    negative    re- 

CH2.N(CH3)3.OH 

suits  when  efforts  are  made  to  oxidize  it  with  potassium  permanganate 
or  with  chromic  acid.  With  concentrated  nitric  acid,  however,  muscarine, 
CHXOH 

\OH  ,  was  easily  obtained.     Like  other  similar  bodies,  this  formula 

CH2.N(CH3)3.OH 

for  muscarine  is  open  to  doubt:  it  probably  has  the  form  of  the  customary  alde- 
hyde: 

CH:0 

I  +H20. 

CH2.N(CH3)3.OH 


24  ORGANIC  SYNTHESES. 

thus  vanillin,  on  exposure  to  the  air,  is  gradually  converted  into 
vanillic  acid;  benzoic  aldehyde,  into  benzoic  acid;  a-naphthoic 
aldehyde,  very  easily  into  a-naphthoic  acid,  etc. 

The  aromatic  aldehydes  are  oxidized  in  the  air  by  fusion 
with  caustic  potash,  and  often  even  by  the  action  of  an  alcoholic 
solution  of  potash.  In  the  latter  reaction  there  is  formed  at 
the  same  time  the  reduction  product  of  the  aldehyde: 

C6H5.C!HJO       KO       C6H5.CO.OK 

T   + 

C6H5.CHO         H          C6H5.CH2.OH 

This  reaction  is  peculiarly  interesting  in  that  it  presents 
an  oxidation  and  a  reduction  proceeding  simultaneously  on  the 
same  substance.  It  seems  rather  difficult  to  understand  just 
how  a  hydrogen  atom  migrates  so  illogically  from  one  mole- 
cule to  another.  It  may  be  that  the  reaction  takes  place  after 
this  fashion: 


C6H5.CH04-£ 


+C6H5CHO 


_C6H5CH2.0!K  _C6H5.CH2.OH 
"  C6H5.CO.OiHrC6H5.CO.OK. 


In  order  to  effect  this  reaction  it  is  necessary  to  employ  a  very 
concentrated  solution  of  caustic  potash,  and  allow  the  mixture 
to  stand  for  several  hours,  taking  care  not  to  allow  the  tem- 
perature to  rise  too  high.  After  diluting  with  water,  the  alcohol 
is  removed  with  ether,  and  the  acid  is  obtained  from  its  aqueous 
solution. 

In  the  paraffin  series  this  reaction  gives  resins  and  con- 
densation products.  Like  the  aromatic  aldehydes,  glyoxal  is 
reduced  by  alcoholic  potash,  giving  glycollic  acid. 

All  the  cases  of  oxidation  which  have  been  met  with  so  far 
may  be  considered  as  a  fixation  of  oxygen,  or  as  a  replacement 
by  OH  of  a  hydrogen  united  to  carbon.  It  has  not  yet  been 
possible  to  fix  oxygen  to  the  carbon  in  unsaturated  compounds, 


OXIDATION.  25 

with  the  exception  of  carbon  monoxide.  By  passing  a  current 
of  strongly  ozonized  dry  air  through  anhydrous  ether,  ethyl 
peroxide  is  formed,  C2H5.O.O.C2H5,  a  liquid  which  decomposes 
on  heating,  and  reacts  with  water  to  form  alcohol  and  hydrogen 
peroxide. 

The  conversion  of  cyanides  into  cyanates  presents  an  ex- 
ample of  changing  from  the  metallic  radical  into  .OM,  analo- 
gous to  the  transformation  of  H  into  .OH. 

If  the  transformation  of  alcohols  into  aldehydes,  etc.,  how- 
ever, is  not  a  simple  removal  of  hydrogen,  there  are  cases  where 
oxygen  causes  the  removal  of  hydrogen.  The  body  then  com- 
bines with  itself;  in  this  manner  there  are  formed  bisulphides, 
pinacones,  etc.,  or  a  double  linking  is  formed  between  two  car- 
bon atoms.  Thus,  by  passing  the  vapor  of  dibenzyl  over 
heated  lead  oxide,  stilbene  is  formed  : 

r\ 


C6H5.CH2  C6H5.CH 

Very  probably  an  intermediate  compound  is  formed  at  first 
which  afterwards  loses  a  molecule  of  water  : 

C6H5.CH2    0     C6H5.CH.;OH_HO    C6H5.CH 

I    —  -        I    !     -^->       II 

C6H5.CH2  C6H5.CH.!H  C6H5.CH 

«• 

The  hydrogen  addition  products  of  the  aromatic  hydrocar- 
bons can  also  lose  their  hydrogen  by  the  action  of  oxidants,  like 
fuming  nitric  acid,  for  instance,  only,  in  place  of  obtaining  the 
aromatic  hydrocarbon,  the  nitro  derivatives  are  produced:  thus, 
C6H4(CH3)2.H6,hexahydride  of  xylene,gives  C6H.(N02)3.(CH3)2. 

In  the  same  manner  the  hydro-pyridine  compounds  lose 
hydrogen  and  pass  into  the  pyridine  derivatives.  For  ex- 
ample, piperidine,  C5HnN,  gives  pyridine,  C5H5.N;  the  hydro- 
chloride  of  conicine,  CsHiyNCsH^H^N.He,  gives  propyl- 
pyridine,  C5H4(C3H7)N. 

The  removal  of  hydrogen  from  nitrogen  compounds  by  oxi- 


26  ORGANIC  SYNTHESES. 

dation  gives  rise  to  a  double  linking  between  two  carbon  atoms, 
between  a  carbon  and  a  nitrogen  atom,  or  between  two 
nitrogen  atoms.1  Thus,  amarine,  C2iHi8N2,  gives  lophine, 
C2iHi6N2,  on  oxidation  with  an  acetic  acid  solution  of  chromic 
acid.  These  two  bodies  can  be  represented  by  the  following 
formulas  : 

C6H5.C.NHX  C6H5.C.NHV 

||        \CH.C6H5-^         ||        >C.C6H5. 
C6H5.C.NH/  C6H5.C.N   ' 

The  primary  amines  of  the  paraffin  series,  on  oxidation  with 
an  alkaline  solution  of  bromine,  yield  nitriles  : 


R.CH2.NH2  --         R.CfeN. 

These  latter  bodies  may  be  converted  again  into  amines  by 
reducing  agents.  Without  doubt,  the  removal  of  hydrogen 
from  the  amines  takes  place  through  the  formation  of  an  inter- 
mediate derivative,  R.CH2.NBr2,  which  subsequently,  by  the 
action  of  the  alkali,  splits  off  2HBr: 


ID 
RCH2.NH2  -    -»  R.CH2.NBr2  -~>  R.CN. 


The  hydrazo  derivatives  are  easily  changed  into  azo-com- 
pounds  : 

R.NH  R.N 


R.NH  R.N 


1  The  oxidizing  action  of  the  air  converts  para-phenylene-diamine,  C6H4<^  J4  j  ]^{j2 

Al)  N  (1)  C6H3/|2)  NH2 

into  tetra-amido-diphenyl-para-azophenylene,  C6H/  }•}'  ^2 

\/l\  >r  ti\  n  XT  /  (  o;  iN±i2 
(D  JN  (1)  ^6M3^(2)  NH^ 

Manganese  dioxide  and  sulphuric  acid,  however,  convert  it  into  quinone,  while, 
-with  bleaching-powder,  it  gives  quinone-dichloride;  para-amidophenol  is  also 
oxidized  in  dilute  solution  by  the  air. 


OXIDATION  27 

This  may  be  brought  about  by  the  action  of  nitrous  acid,  mer- 
cury oxide,  chlorine,  bromine,  ferric  chloride,  Fehling's  solution, 
etc.  In  many  cases  simply  atmospheric  oxygen  is  sufficient. 

The  hydrazines  also  give  diazo  derivatives;  thus,  the  salts 
of  phenyl-hydrazine,  with  mercuric  oxide,  are  changed  into  the 
salts  of  diazo-benzene  : 

C6H5.NH-NH2.HX—  2H2  =  C6H5N  =  NX. 

In  some  cases,  oxidation  is  accompanied  by  a  hydration, 
especially  with  unsaturated  compounds.  One  would  think  that 
in  most  cases  the  action  of  oxidizing  agents  in  such  bodies- 
would  be  to  break  up  the  double-linking;  but  from  recent  re- 
searches (principally  those  of  Wagner)  it  would  seem  that  these 
bodies,  when  oxidized  by  potassium  permanganate,  preserve 
the  integrity  of  their  molecule,  and  that  the  rupture  is  only  due 
to  the  oxidation  which  is  continued  on  the  bodies  formed  in  the 
first  place.  According  to  this,  there  would  occur  in  unsaturated 
compounds  the  fixation  of  0  +  H20,  that  is  to.  say,  the  elements 
of  hydrogen  dioxide,  or  2  (OH).1 

It  is  in  this  manner  that  the  unsaturated  hydrocarbons 
CTCH2n  are  transformed  into  glycols,  and  the  unsaturated 
alcohols  CnHjnO  into  glycerols: 

CH2.OH  CH2.OH    CH2    n  ,  „  n      CH2.OH 


CH          0  +  H20        CH.OH      CH2  CH2.OH 

II  ~*    I 

CH2  CH2.OH 

The  yield  of  glycol  is  about  50  per  cent,  of  the  theoretic 
quantity;  it  may  be  increased  by  taking  a  weaker  oxidant. 
This  is  the  simplest  manner  of  obtaining  the  higher  glycols. 


1  See  Wagner,  Action  of  Oxidants,  etc.  This  kind  of  reaction  is  very  simi- 
lar to  that  of  A.  Zaytzeff,  who  admits  the  formation  of  an  oxide  and  the  sub- 
sequent fixation  of  a  molecule  of  water.  It  is  known,  besides,  the  oxygenated 
water  (OH)2  comb  nes  directly  with  ethylene,  giving  ethylenic  glycol. 


28  ORGANIC  SYNTHESES. 

In  the  researches  of  Wagner,  the  method  of  procedure  was 
as  follows:  30  grams  of  the  hydrocarbon  are  placed  in  a  large 
flask  with  a  litre  of  water,  and  vigorously  agitated,  while  adding 
about  5  litres  of  a  1  per  cent,  solution  of  potassium  perman- 
ganate. The  proportions  should  be  such  that  there  is  1  atom 
of  oxygen  for  1  molecule  of  the  hydrocarbon,  and  1.5  to  2  atoms 
for  higher  numbers. 

The  action  of  potassium  permanganate  on  the  hydrocarbons 
Cn  H2n  furnishes  a  good  means  of  establishing  their  constitution. 

The  oxidation  of  the  alcohols  CnH2nO  with  potassium 
permanganate  gives  trihydric  alcohols.  The  hydrocarbons,  with 
two  double  bonds  CnH2n-2,  as,  for  instance,  diallyl,  are  con- 
verted into  tetrahydric  alcohols  by  reason  of  the  fixation  of 
02+2H20=(OP)4. 

The  unsaturated  hydrocarbons  and  acids  are  easily  changed 
into  saturated  acids  by  the  action  of  potassium  permanganate. 
A.  Zaytzeff  1  has  shown  that  oleic  acid,  CigH3402,  is  transformed 
into  dioxy-stearic  acid,  Ci8H34(OH)202.2  From  fumaric  acid 
in  the  same  manner  is  prepared  tartaric  acid.3 

The  supposition  may  be  made  that  in  this  transformation 
of  unsaturated  acids  into  saturated  ones,  for  example,  of  palmi- 
tolic  acid  Ci6H2802  into  oxy-palmitolic  acid,  Ci6H2804,  there  is 
not  a  fixation  of  02,  but  a  combination  with  (OH)4,  accom- 
panied by  a  liberation  of  2H20. 

Wagner  thus  gives  an  explanation  of  the  interesting  fact  of 
the  change  of  non-symmetrical  ethylene  dibromide  into  brom- 
acetyl-bromide  CH2Br.CO.Br,  observed  by  Demole. 

.  l  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  17,  p.  417. 
2  Ibid.,  vol.  24,  pp.  13-27. 

3S.  Tanatar,  On  the  Constitutional  Formula  of  Fumaric  and  Oleic  Acids. 
See  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  13  (2),  p.  256. 


OXIDATION  29 

B.  Direct  Oxidation  Accompanied  by  Decomposition  of  the 

Molecule. 

This  series  of  reactions  includes  the  influence  of  oxidants 
on  tertiary  alcohols,  polyhydric  alcohols,1  ke tones,  and  many 
aromatic  compounds. 

The  oxidation  of  tertiary  alcohols  takes  place  with  fixation 
of  0  +  H20;  the  two  groups  which  are  the  richest  in  hydrogen 
remain  in  combination  with  the  C.OH  group,  while  the  third 
radical  is  split  off  and  is  subjected  to  a  further  oxidation. 

Thus,  in  the  oxidation  of  trimethyl-carbinol  there  is 
obtained  acetone  and  carbon  dioxide : 


CH3\  /|CH3    OH     +03     -2H20==CH3\          C02 
CH3/^\OH  +OH  -  H20    CHa/*'    4 


Dimethyl-ethyl-carbinol,  under  the  same  conditions,  gives 
acetone  and  acetic  acid: 

(CH3)2C.OH  OH        -H20        (CH3)2.CO 

.....  I  .....  + 

CH2.CH3      OH  +  02-H20        CH3.CO.OH 


with  isopropyl-dimethyl-carbinol;    two   molecules  of  acetone 
are  obtained: 

.C.OH  OH       -  H20  =  (CH3)2CO. 

-H20  =  (CH3)2CO. 


The    acid-alcohols    behave    in    the    same    manner  as  the 

tertiary  alcohols. 

/OTT 
Thus,  with  the  tertiary  acid-alcohol,  R2C<^  QQQ  jj>  the  ketone 


1  Prjibuitek,  On  Some  Oxidation  Products  of  the  Polyatomic  Alcohols.  St. 
Petersburg,  1881  (in  Russian).  By  the  oxidation  of  erythrite  with  potassium 
permanganate,  oxalic  acid  was  obtained. 


3°  ORGANIC  SYNTHESES. 


COOH' 
the  aldehyde  R.CHO  is  formed: 

R2.C.OH       OH  -  H20  =  R2.CO 

I  + 

CO.OH    OH-H20  =  C02 


:Nc.OH       OH  -  H20 = R.CH.O 

Xl  + 

CO.OH    OH-H20  =  C02 


Certain  acids  of  the  preceding  general  formula  are  sometimes 
oxidized  and  still  preserve  the  integrity  of  their  molecule. 

The  decomposition  of  the  unsaturated  hydrocarbons  by 
the  action  of  oxidants  is  merely  the  result  of  a  further  oxidation 
of  the  first  products  formed.  Bv  fusing  with  caustic  potash, 
for  instance,  some  of  the  acids  of  the  acrylic  series  undergo  an 
oxidation  simultaneous  with  their  reduction.  Also,  isobutylene 
on  oxidation  gives  a  glycol,  which  further  yields  an  hydroxy- 
acid,  and  the  latter  is  decomposed  into  a  ketone  and  an  acid: 

(CH3)2.C         OH  (CH3)2.C.OH     (CH3)2.C.OH 

II       +  >  I 

CH2     OH  +  02-H20  CH2.OH  CO.OH 

(CH3)2C.   OH    .OH-H20    (CH3)2.CO 
CO.OH    'OH-H20    C02 

If  the  oxidation  takes  place  in  the  presence  of  an  acid,  a 
glycol  is  formed,  which  then  loses  a  molecule  of  water,  and  by  a 
further  oxidation  gives  abnormal  products. 

Cinnamic  acid,  C6H5.CH:CH.COOH,  for  example,  should 
give  at  first,  on  oxidation,  a  di-acid  alcohol,  and  this  latter  body 
is  subsequently  converted  into  benzaldehyde  and  glyoxylic 
acid: 


OXIDATION.  31 

C6H5.  CH  C6H5.  CH.OH  C6H5.CHO 


COOH.CH  HOH     COOH.CH.OH      OH     CH(OH)2.COOH 

These  finally  are  converted  by  oxidation  into  benzoic  acid 
and  oxalic  acid.  These  reactions  serve  as  a  means  of  detecting 
the  presence  of  cinnamic  acid,  it  being  recognized  by  evolving 
the  odor  of  benzaldehyde  when  heated  with  Pb02.  It  might 
be  noted  that  this  method  of  oxidation  frequently  causes  a 
division  of  the  molecule.1  Glycol,  for  instance,  in  dilute  alka- 
line solution,  when  treated  with  lead  peroxide,  gives  formic 
acid  with  a  simultaneous  evolution  of  hydrogen  gas  : 

CH2.OH      PKn       H.COOH 

I  rPU2  ,   TT 

--  >  +Jti2. 

CH2.OH  H.COOH 

Alcohol,  cane-sugar,  and  other  such  compounds  behave  in  a 
similar  manner,  yielding  the  same  products: 

CH3  PKn       H.COOH 

|  _L^L2_>  +H2. 

CH2.OH  H.COOH 

Ortho-nitrobenzaldehyde  may  be  conveniently  prepared  from 
cinnamic  acid.  The  solution  of  the  latter  is  poured  into 
benzene,  and  there  is  added  with  constant  stirring  a  dilute 
solution  of  potassium  permanganate.  The  aldehyde  at  first 
formed  passes  into  solution  in  the  benzene,  and  is  thus  preserved 
from  further  oxidation.  This,  in  fact,  is  a  good  general  method 
for  protecting  easily  oxidizable  products  from  being  decomposed 
by  successive  oxidation.  After  each  addition  of  the  oxidant, 
the  liquid  should  be  well  shaken  or  stirred,  in  order  to  remove 
the  aldehyde  as  much  as  possible  from  the  further  oxidizing 
influence  of  the  potassium  permanganate. 

1  Thus  uric  acid  gives  allantoin. 


32  ORGANIC  SYNTHESES. 

Ke tones  are  oxidized  with  hydrolysis;   that  is  to  say,  there 
is  a  fixation  of  0  +  H20  =  (OH)2.    For  example : 


CHg.CO 

1      _J. 

OH                      CH3.CO.OH 

CH3.CH2 

CH3.CO 

|     _|_ 

OH  +  02-H20    CH3.CO.OH 
OH                     CH3.CO.OH 

(CH3)2.CH 

(CH3)3.C.CO 

1       _i_ 

OH  +  0-H20    (CH3)2.CO 
OH                      (CH3)3.C.CO.OH 

1        ' 
CH3 

OH  +  02-H20    H.CO.OH 

The  oxidation  of  ketones  is  a  more  complicated  reaction 
than  would  at  first  sight  appear.1  In  fact,  the  products  which 
are  obtained  are  dependent  upon  the  nature  of  the  oxidant 
and  the  circumstances  of  the  reaction.  Thus,  with  chromic 
acid  mixture,  there  is  usually  obtained,  not  two,  but  four, 
compounds;  the  decomposition  taking  place  in  two  different 
directions,  on  account  of  the  oxidation  of  the  two  CH3  groups 
attached  to  the  CO.  We  have  a  proof  of  it  in  the  oxidation 
of  ethyl-isobutyl-ketone  :  the  principal  products  formed  are 
acetic  and  isovaleric  acids,  while,  at  the  same  time,  prop^onic 
and  isobutyric  acids  are  produced  : 


\  +  OH+02-H20-CH3.CO.OH 
(CH3)2CH.CH2  +OH  =  (CH3)2.CH.CH2.CO.OH 

CH3.  CH2\m    +OH  _  =CH3.CH2.CO.OH 
<CH3)2.CH.CH2/^/+OH+02-H20=(CH3)2.CH.CO.OH 

One  form  of  the  decomposition  always  predominates  over 
the  other.  That  found  in  the  example  given  above  is  exactly 
contrary  to  the  ideas  of  Popoff.  In  some  ketones,  where  the 

1  More  so  than  is  included  in  Popoff's  law  of  oxidation.  See  A.  Popoff,  On 
the  Oxidation  of  Ketones,  Kazan,  1869;  and  On  the  Normal  Oxidation  of  Ketones, 
Warsaw,  1877.  See  also  Wagner,  Synthesis  and  Oxidation  of  the  Secondary 
Alcohols,  St.  Petersburg,  1885.  (All  of  these  in  Russian.) 


OXIDATION.  33 

two  atoms  of  carbon  linked  to  the  CO  group  do  not  have  hydro- 
gen, oxidation  takes  place  without  rupture  of  the  molecule,  and 
with  the  formation  of  a  ketonic  acid,  C6H5.CO.C6H4.CH3,  is 
oxidized  to  C6H5.CO.C6H4.CO.OH. 

The  temperature  has  an  influence  on  the  character  of  the 
reaction.  In  the  cold,  methyl-butyl-ketone  with  potassium 
permanganate,  or  chromic  acid,  gives  only  butyric  and  acetic 
acids;  if  heat  is  employed,  there  is  formed  an  acid  containing 
more  carbon  atoms  (probably  valeric  acid). 

Similarly  to  the  ketones,  the  ketonic  acids  are  decomposed 
according  to  the  following  reaction : 

R  +  OH=R.OH 


r»n/  i  rkTT_v/ CO.OH 

UJ\X.CO.OH+       ~A\CO.OH 

The  group  R.OH  then  undergoes  a  further  oxidation.  The 
higher  fatty  acids  are  decomposed  by  oxidation  into  mono- 
and  di-carboxylic  acids,  with  the  constant  and  characteristic 
formation  of  succinic  acid.  The  silver  salts  of  the  fatty  acids 
are  partially  decomposed  on  dry  distillation;  this  decomposition 
may  be  represented  by  the  equation : 

2nCnH2n_102Ag=(2n-l)CnH2n02+C02  +  (n-l)CH-2nAg. 

The  salts  of  diatomic  acids,  such  as  fumaric  acid,  are  entirely 
decomposed  by  iodine.  The  oxygen  liberated  oxidizes  the 
anhydride  found  in  accordance  with  the  equation : 

C4H204Ag2  + 12  =  2AgI + C4H203  +  0. 

Caproic  acid,  CH3.CH2.CH2.CH2.CH2.CO.OH,  with  nitric 
acid,  gives  acetic  and  succinic  acids;  from  oenanthylic  acid,  CHa.- 
€H2.CH2.CH2.CH2.CH2.CO.OH,  propionic  and  succinic  acids 
are  obtained.  It  is  probable  that  ketonic  acids  are  formed, 
which  are  further  decomposed  according  to  the  equation: 


34  ORGANIC  SYNTHESES. 

2.CH3  +  OH  +  02.  -  H20 = CH3.CO.OH 

)H2.CH2.CO.OH  +  OH  CH2.CO.OH 

CH2.CO.OH 


It  is  possible  that  the  decomposition  of  different  aromatic 
hydrocarbons  by  oxidation  may  proceed  with  the  formation  of 
ketones.  All  that  is  known  is,  that  the  oxidation  of  ethyl 
benzene,  C6H5.CH2.CH3,  gives  the  ketone  C6H5.CO.CH3r 
acetophenone. 

The  oxidation  of  naphthalene  into  phthalic  acid,  as  expe- 
rience proves,  does  not  take  place  directly,  but  a  ketonic  acid 
is  formed  as  an  intermediate  product: 


/CO.CO.OH  /PO 

/  n  TJ  /  t>U 

\  >    t6il4<    p0 

CH  XXXOH  \CO 


The  best  oxidant  to  employ  is  a  chromic  acid  mixture :  the 
acetic  acid  solution  of  chromic  acid  gives  principally  the  naphtho- 
quinone  CioH602.  Quinoline,  C4H4.C5H3N,  behaves  hke  naph- 
thalene and  gives  pyridine  dicarboxylic  acid  (COOH)2.C5H3N. 

It  has  been  shown  that  in  the  oxidation  of  aromatic  hydro- 
carbons, the  groups  CnH2n+i,  like  CH3,  are  converted  into 
carboxyl,  COOH;  the  group  C6H5  behaves  in  a  like  manner, 
and  thus  diphenyl  gives  benzoic  acid: 


C6H5.C6H5  -^-»  C6H5.CO.OH. 

The  oxidation  of  additive  hydrogen  aromatic  compounds  gives 
some  interesting  results:  quinic  acid,  C6H7(OH)4CO.OH,  with 
manganese  dioxide  and  sulphuric  acid,  is  converted  into  qui- 


OXIDATION.  35 

none;  it  was  in  this  manner  that  the  latter  was  discovered  by 
Woskresenky.1  The  hydrochloride  of  a-tctra-hydro-naphthyl- 
amine,  NH2.C10H7.H4;  with  permanganate,  gives  adipic  acid, 
€6Hi004  (yield,  about  18  per  cent). 

Benzene  with  potassium  chlorate  and  sulphuric  acid  gives 
j3-trichlor-acetyl-acrylic  acid,  CC13.CO.CH=CH.CO.OH  (also 
called  trichlor-phenomalic  acid),  which  has  been  wrongly  taken 
for  trichlor-hydroquinone. 

The  azo  derivatives  are  oxidized  with  a  decomposition  of 
their  molecule.  It  is  probable  that  azo-benzene,  C6H5N: 
N.C6H5,2  heated  for  some  time  in  a  sealed  tube  with  an  acetic 
acid  solution  of  chromic  acid,  is  converted  into  nitrobenzene, 
C6H5.N02(?).3 

IV.  INDIRECT  OXIDATION. 
A.   Substitution  of  a  Halogen  by  the  Hydroxyl  Group.4 

This  reaction,  which  results  in  the  formation  of  an 
alcohol,  may  be  brought  about  by  the  action  of  water 
alone;  generally  it  is  necessary  to  heat  in  a  sealed  tube.  If 
the  alcohol  formed  is  soluble  in  water,  it  may  be  isolated  by 
means  of  potassium  carbonate.  Tertiary  compounds  more 
easily  give  up  the  halogen  than  do  the  secondary  compounds; 
and  these,  in  turn,  more  readily  than  the  primary  compounds. 

1  A.   Woskresensky,  On  Quinic  Acid  and  the  Discovery  of  a  New  Product, 
Quinone,  St.  Petersburg,  1839  (in  Russian). 

2  Petrieff,  Data  for  the  Study  of  Azo-Benzene,  Odessa,  1872  (in  Russian). 

3  See  Jour.  Soc.   phys.  Chim.  Eusse,  vol.   18,  p.   387. 

4  The  conversion  of  primary  alcohols  into  aldehydes  by  the  oxidizing  action 
of  chlorine  is  no  doubt  an  indirect  reaction,  there  first  being  a  substitution  of 
hydrogen  by  chlorine  and  then  a  subsequent  splitting  off  of  hydrochloric  acid: 


I >    CH3.CH:0+HC1. 

The  formation  of  chloral  from  ethyl  alcohol  may  be  explained  in  this  way,  there 
also  occurring  a  simultaneous  substitution  of  the  hydrogen  of  the  CH3  group 
by  chlorine. 


36  ORGANIC  SYNTHESES. 

For  example,  tertiary  amyl  iodide  is  easily  converted  into  the 
corresponding  alcohol  by  agitation  with  cold  water : 

(CH3)2.(C2H5)C.I  JMU  (CH3)2(C2H5).C.OH. 

Triphenyl-brom-me  thane,  (C6H5)3.C.Br,  behaves  in  the  same 
manner.  Isopropyl  iodide,  (CH3)2,CHI,  however,  is  only  con- 
verted into  isopropyl  alcohol,  (CH3)2.CH.OH,  after  a  long 
heating  under  pressure  with  a  large  quantity  of  water.  And 
the  conversion  of  isobutyl  iodide  (CH3)2:CH.CH2I,  or  of  primary 
isoamyl  chloride  (CH3)2CH.CH2.CH2.C1,  takes  place  with  even 
greater  difficulty.  Isobutyl  iodide,  however,  with  silver  oxide 
and  water,  instead  of  giving  the  corresponding  alcohol,  gives 
tertiary  butyl  alcohol. 

This  method  of  obtaining  alcohols  is  only  applicable  in 
cases  where  the  halogen  compound  does  not  easily  form  an 
unsaturated  body  through  the  splitting  off  of  hydrochloric 
acid.  In  all  cases,  however,  it  is  best  to  use  an  excess  of  water 
in  order  to  prevent  the  formation  of  an  unsaturated  body. 
For  instance,  a-hexyl  iodide  with  a  small  amount  of  water 
gives  hexylene  and  hydriodic  acid;  with  a  large  excess  of  water  r 
it  furnishes  the  alcohol,  CH3.(CH2)3.CH.(OH)CH3.  Some- 
times, secondary  products  are  formed;  on  heating  ethyl  bromide 
with  a  little  water  to  200°  C.,  ethyl  oxide  is  formed,  at  the 
same  time  as  ethylene,  C2H4,  and  hydrobromic  acid,  from  the 
further  action  of  the  ethyl  bromide  on  the  alcohol. 

In  decomposing  the  iodides,  sealed  tubes  may  be  avoided 
by  the  use  of  oxides  (PbO,  Ag20,  HgO),  barium  hydrate 
(Ba(OH)2),  or  the  carbonated  alkalies,  K2C03  and  Na2C03. 
Silver  oxide  is  particularly  good  for  those  iodides  which  easily 
give  unsaturated  compounds,  for  the  reaction  then  takes  place 
without  the  necessity  of  heating.  The  other  hydrates  and 
carbonates  only  act  well  on  boiling,  and  always  lead  to  the 
formation  of  unsaturated  compounds.  In  certain  cases,  when, 
these  latter  cannot  be  formed,  the  substitution  of  a  halogen  by 
OH  is  effected  by  the  aid  of  the  hydrates  of  the  alkaline  metals.. 


OXIDATION.  37 

<C1 
COOH'  w*^  Potassium  nv~ 


drate,  is  converted  into  glycollic  acid, 

If  there  are  several  halogen  atoms  present  in  the  molecule, 
they  are  usually  all  replaced  together,  whether  they  are  fixed 
to  a  single  carbon  atom  or  to  several  carbon  atoms.  Thus, 
benzylidene  chloride,  CeHs.CH.C^,  gives  benzaldehyde, 
CeH5.CHO  (the  best  process  is  to  heat  with  anhydrous  oxalic 
acid).  The  a-dichlor-propionic  acid  behaves  in  the  same 
manner.  Phenyl-chloroform,  CeHs.C.Cls,  with  water  at  150°  C.y 
very  readily  yields  benzoic  acid,  C6H5.COOH;  and  the  action 
of  soda  on  the  ether  of  trichlor-lactic  acid,  CC13.CH(OH).COOH, 
is  the  most  convenient  method  for  the  preparation  of  tartronic 
acid,  CH.(OH)  (CO.OH)2.  In  the  same  way,  ethylene  chloride, 
CH2.C1 

|  ,  gives  glycol,  and  trichlor-hydrin,  CH2CLCH.CLCH2Clr 

CH2.C1 

with  20  parts  of  water  at  160°  C.,  gives  glycerol.  Occasionally, 
however,  when  CnH2nBr2  is  heated  with  water,  instead  of 
obtaining  the  corresponding  glycol,  an  aldehyde  or  a  ketone  is 
produced.  Sometimes  all  of  the  halogens  cannot  be  removed; 
dibrom-proprionic  acid,  CH2Br.CHBr.COOH,  on  boiling  with 
water  and  silver  oxide,  is  only  converted  into  brom-hydracrylic 
acid,  CH2(OH).CH.Br.CO.OH. 

For  the  preparation  of  glycols,  especially  the  lower  homo- 
logues,  the  halogen  compound  may  be  boiled  with  a  large 
excess  of  water,  and  the  theoretic  quantity  of  carbonate  of 
potash  with  an  inverted  condenser.  With  water  alone,  the 
reaction  proceeds  slowly,  and  only  when  heated  under  pressure. 
The  yield  is  increased  with  the  quantity  of  water,  but  it  is 
difficult  to  obtain  50  per  cent,  of  the  theoretical  amount,  as 
there  is  always  a  part  of  the  compound  which  is  changed  into 
an  unsaturated  body. 

The  introduction  of  OH  can  be  made  in  a  simple  manner 
by  the  action  of  a  silver  salt  (or  of  another  metal)  on  any  of 

f 


38  ORGANIC  SYNTHESES. 

the  acids;  in  this  manner  an  ester  is  at  first  obtained  which  is 
subsequently  saponified. 

During  the  replacement  of  a  halogen  by  OH  in  the  sub- 
stituted carboxylic  acids,  hydrochloric  acid  is  often  evolved. 
The  best  results  are  obtained  by  a  long-continued  heating  with 
water  alone. 

When  the  halogen  occurs  in  the  benzene  ring,  in  order  to 
replace  it  with  OH,  it  is  necessary  to  fuse  with  potash.  Mono- 
iodo-benzene,  however,  by  this  method  does  not  give  a  trace 
of  phenol. 

The  displacement  occurs  more  readily  if  the  compound 
contains,  next  to  the  halogen  atom,  another  halogen  atom,  or 
one  of  the  groups  OH,  N02,  or  COOH.  Thus,  dibrom-toluene, 

/(I)  CH3 

C6H3(-(3)  Br   with  a  little  water  in  a  sealed  tube,  gives  orcinol, 
\(5)  Br 

/(1)CH8  /mT 

C6H3^(3)  OH.    Ortho-iodo-phenol,  C6H4<  }*{  *        on   fusion 
\5)  OH 

with  potash,  gives  pyrocatechol,  C6H4<^  L\  QH' anc*  meta"c^or" 

benzoic  acid  gives  meta-oxy-benzoic  acid.  Hexachlor-benzene, 
Cede,  heated  with  glycerol  and  caustic  soda,  is  converted  into 

C6C15OH,  and,  with  water  at  200°  C.,   into  CJB^S)  OH> 

pyrocatechol. 

It  often  happens  in  these  fusions  with  potash  that  there  is 
a  molecular  transformation,  either  by  reason  of  too  prolonged 
an  action  or  too  high  a  temperature.  The  ortho-  and  meta- 
bromphenols,  when  fused  with  potash,  both  give  pyrocatechol 

and  resorcinol,  CeEL^  /  J  QJJ-    The   alkali   during   the   fusion 

behaves  at  times  as  a  reducing  agent  and  again  as  an  oxidant; 
and  thus  it  is  possible  to  explain  the  molecular  transposition 
by  two  successive  reactions  of  oxidation  and  reduction.  The 

ortho-bromphenol,  C6H4<^ L)  Br>  is  at  first  transformed  into 


OXIDATION.  39 

/(I)  OH 
€6H3(-(2)  Br  ,  and  then  into  resorcinol.  C6H4<  )i<  Xti. 

\3)  OH 

The  presence  of  the  N02  group  facilitates  the  exchange  of 
halogens  with  OH,  especially  when  the  two  substituents  are  in 
the  ortho  (1:2)  or  meta  (1:3)  positions.  In  the  latter  case  the 

influence  is  so  great  that  the  nitro-chlor-benzene,  C6H4<f  ;*;  ^1 

N02J 


may  be  transformed  into  ortho-nitrophenol,   C6H4^  ;0c  Mn  , 


by  gently  heating  with  an  alkali.     If  there  are  two  nitro  groups, 
boiling  with  sodium  carbonate  is  sufficient  to  replace  a  halogen 
with   the   OH  group;    as,  for  example,  with  dichlor-dinitro- 
XI)  Cl 

/_/9\    "NJQ 

benzene,  C6H2  _  ,*{  ™   2,  which,  under  the  conditions   men- 

\6)  N02 

/d)  OH 
tioned,   gives   chlor-dinitro-phenol  :     C6H2H^  ™  2.     It  may 

^(6)  N02 

happen  with  chlor-nitro-compounds,  if  there  are  several 
N02  groups,  that  one  of  these  may  also  be  exchanged  for 
OH. 

Among  the  other  aromatic  compounds,  which  readily  ex- 
change their  halogen  groups  for  others,  are  to  be  noticed  the 
brom-anthraquinones,  and  the  halogen  derivatives  of  quinoline 
(in  the  pyridine  nucleus).  Thus,  mono-brom-anthraquinone, 

^  pri  yCeHaBr,  on  fusion  with  potash  at  a  moderate  tem- 


perature,  gives  monoxy-anthraquinone,  C6H4<^  ^Q  yC6H3OH. 
The  oxidation  is  the  more  complete  as  the  temperature  is  more 

elevated.    The  a-chlor-quinoline,  |  ]    ,  is  distinguished 


N 
from  its  isomers  in  that,  when  heated  with  water  at  120°  C.,  it  gives 


4°  ORGANIC  SYNTHESES. 

/\/\OH 

;  while  the  /?-  and  f-chlor-quinolines  undergo  no 

N 
change  even  when  heated  with  potash  at   220°  C. 

The  chlorides  of  the  organic  acids,  such  as  benzoyl  chloride r 
C6H5.CO.C1,  and  acetyl  chloride,  CH3.CO.C1,  readily  exchange 
their  Cl  for  OH  by  the  action  of  water. 

The  chlorides  of  the  sulphonic  acids  are  very  stable  in  their 
behaviour,  and  in  order  to  transform  them  into  their  correspond- 
ing acids  it  is  necessary  to  subject  them  to  prolonged  boiling 
with  water,  or,  in  order  to  accelerate  the  reaction,  with  metallic 
hydrates  or  oxides. 

In  compounds  analogous  to  (CH3)SI,  the  halogen  may  be 
replaced  by  OH  with  the  aid  of  recently  prepared  hydrated 
oxide  of  silver.  Halogens  united  to  nitrogen  behave  in  the 
same  manner : 

2(CH3)4NI + Ag20  +  H20  =  2(CH3)4N.OH +2AgI. 

The  chlorine  derivatives  of  amines  are  not  as  readily  decom- 

/CH2.CeH5. 
posed   as   the   iodine   compounds.      Thus:    N(Cl)r-C6H5 

NCH8)a 

(formed  by  the  action  of  benzyl  chloride  on  dimethylaniline) 
is  not  at  all  converted  into  the  corresponding  hydrate  by  the 
action  of  moist  silver  oxide.  In  this  particular  case  it  is  neces- 
sary to  prepare  the  sulphonic  derivative,  which  is  then  decom- 
posed with  the  theoretical  amount  of  baryta.  In  a  salt  of  an 
amine,  when  a  halogen  is  united  to  carbon,  it  may  be  replaced 
by  OH  by  the  aid  of  moist  silver  oxide,  or  may  even  be 
eliminated  in  the  form  of  its  hydrogen  acid: 


OXIDATION.  41 


B.  Oxidation  by  the  Use  of  Ammonia  Derivatives. 

The  displacement  of  NH2  by  OH  (from  bases  or  from  acids) 
is  brought  about  by  the  action  of  nitrous  acid. 

The  nitrites  of  the  amines  behave  like  the  nitrite  of  am- 
monia  when  heated  with  water  : 

NH4.N02  =  N2  +  H.OH  +  H20. 
R.NH3.N02  =  N2  +  R.OH  +  H20. 

In  order  to  transform  NH2  into  OH,  the  nitrite  of  the  amine 
is  first  prepared  (by  double  decomposition  of  the  hydrochloride 
with  silver  nitrite,  AgN02),  then  subsequently  decomposed  by 
heat;  or,  further,  by  treating  the  amine  with  nitrous  oxide, 
N203,  in  the  presence  of  water,  until  nitrogen  ceases  to  be 
evolved. 

The  amines  of  the  paraffin  series  often  give  secondary 
products.  Thus,  normal  butyl-amine,  C3H7.CH2.NH2,  besides 
normal  butyl  alcohol,  C3H7.CH2.OH,  also  gives  secondary  butyl 
alcohol,  CH3.CH2.CH/£H3j  butylene,  CH3.CH2.CH  =  CH2,  and 

(C4H9)2.N.NO. 

In  the  benzene  derivatives  the  reaction  is  brought  about  by 
heating  any  salt  of  the  azo  compounds  with  water. 

A  good  yield  of  meta-chlor-phenol  (1:3)  may  be  obtained 
in  the  following  manner  :  Dissolve  in  water  the  nitrate  of  meta- 


chlor-aniline,    CA  2.8j   CQol  well>  and  saturate 


with  a  current  of  N203  gas;  on  adding  a  cold  concentrated 
solution  of  mercuric  chloride,  HgCl2,  a  double  compound  of 
mercury  separates  out,  which  is  subsequently  decomposed  by 
boiling  with  water  until  nitrogen  ceases  to  be  evolved.  Soda  is 
added;  the  oxide  of  mercury  is  filtered  off;  the  filtrate  is  acidu- 
lated, and  the  chlor-phenol  is  separated  by  dissolving  in  ether. 
The  same  method  of  making  phenols  may  also  be  used  in 
the  preparation  of  oxy-phenols,  the  chlor-  and  nitre-derivatives,. 


42  ORGANIC  SYNTHESES. 

the  oxy-aldehydes,  oxy-ke  tones.  Certain  of  the  brom-  and 
chlor-amines  present  exceptions  to  the  usual  procedure,  the 
NH2  being  replaced  by  H  instead  of  OH.  Thus,  the  diazo- 

/(2)  Br 
compound  of    dibrom-anilLne,  C6H3^-(1)  NH2,   when  decom- 

\(4)  Br 
posed   by    boiling   with   water,    gives   di-brom-benzene;     the 

/(I)  CH3 

chlor-toluidine,  CeH3^-(3)  Cl     ,  in  place  of  chlor-cresol  gives 
\(4)  NH2 

/"»TT 

* 


chlor-toluene,  Ce^     /     ^ 

The  NH2  group  in  acid  amides  of  amido-carboxyl  and 
.amido-sulphonic  acids  is  very  resistant  to  the  action  of  nitrous 
acid,  N203.1  Thus,  the  amides  of  the  meta-  and  para-amido- 

benzoic  acids,    CeH^  ^Q  ^TTT  ,   through  the  medium  of  the 


diazo  reaction,  are  converted  into  CeEUQQ^jj  ,  but  the  group 
CO.NH.2  remains  unchanged;  the  amide  of  the  ortho-amido- 
sulphonic  acid  of  benzene,  CeEL  J  2  ,  behaves  in  the 


same  way. 

If  a  very  negative  element  or  radical  occurs  with  the  NH2 
group,  the  latter,  by  the  action  of  alkalies,  is  often  converted 
into  OH  with  the  elimination  of  ammonia.  Many  aromatic 
amido  compounds  in  which  the  NH2  is  in  the  ortho-  or  para- 
position  to  N02  behave  in  this  manner.  For  example,  para- 

jiitro-aniline,  C6H4</  2,   with    potash,  gives    para-nitro- 


,        i   n  TT  /(I)  OH 
phenol,  C6H4<  >4<  NQ  . 


1  If  there  is  no  NH2  group  in  the  aromatic  nucleus,  then  it  is  the  SO2-NH2 
group  which  is  attacked  by  the  nitrous  oxide.     Thus: 

2  conTCrted  into  C«H<(3)  f§.OH 


OXIDATION.  43 

The  NH2  group  when  joined  to  CO,  is  easily  converted  into 
OH  by  the  action  of  acids  or  alkalies.  The  acid  amides  are 
thus  changed  into  carboxylic  acids.  Formamide  with  concen- 
trated caustic  potash,  even  in  the  cold,  gives  potassium  formate 
with  liberation  of  NH3.  In  other  cases  it  is  necessary  to  boil 
with  the  alkali  for  a  prolonged  time  in  order  to  liberate  all  of 
the  ammonia.  In  place  of  potash,  soda  may  be  used,  or  even 
barytes  or  caustic  lime.  The  NH2  group  in  acid  amides  is 
converted  into  OH  by  the  action  of  nitric  acid.  Thus, 
CH3.CO.NH2  +  N02.OH  =  CH3.CO.OH  +  N20  +  H20.  Substituted 
acid  amides,  such  as  methyl-acetamide,  behave  in  the  same 
manner.  By  the  action  of  nitric  acid  on  dimethyl-acetamide, 
there  is  formed,  at  the  same  time  with  the  acetic  acid,  dimethyl- 
nitramine  : 


The  amides  of  the  di-acids,  by  the  action  of  boiling  ammonia, 
are  converted  into  the  amido-ammonium  salts.  For  example: 

CO.NH2  CO.NH2 

I  —  »     I 

CO.NH2  CO.ONH4 

Oxamide.  Ammonium  oxamate. 

If  alkalies  act  but  slowly  on  acid  amides,  they  may  be 
heated  in  a  sealed  tube  with  concentrated  hydrochloric  acid. 
With  the  keto-amides  R.CO.CO.NH2,  however,  it  is  necessary 
to  operate  with  caution,  for  they  are  easily  decomposed: 
(CH3)2.CH.CO.CO.NH2,  by  the  moderate  action  of  hydro- 
chloric acid,  furnishes,  simultaneously  with  the  acid,  (CH3)2. 
CH.CO.CO.OH,  considerable  iso-butyric  acid,  (CH3)2.CH.COOH. 

The  amides  of  sulphonic  acids,  on  treatment  with  hydro- 
chloric acid  at  150°  C.,  are  converted  into  sulphonic  acids; 
if  the  reaction  is  energetic  it  may  even  happen  that  the 
S02.OH  group  is  removed.  The  S02NH2  group  is  very  resist- 
ant to  alkalies. 


44  ORGANIC  SYNTHESES. 

The  transformation  of  >N.OH  into  O  takes  place  by  the 
action  of  concentrated  hydrochloric  acid  on  the  iso-nitroso- 
compounds  and  aldoximes,  heating  if  necessary;  a  weaker 
acid,  such  as  acetic,  may  also  be  used: 

CH3.C=N.OH  CO.CH3 

|  +  H20  =      |  +NH2.OH 

CH2.CH2.CO.OH  CH2.CH2.CO.OH 

7-iso-nitroso-valeric  acid.  ^-acetyl-propionic  acid. 

Iso-nitroso  bodies  are  decomposed  in  the  same  manner  by 
the  action  of  amyl  nitrite  : 


C6H5.CO.CO.CH3  +  C5Hi  !.OH  +  N20. 

The  transformation  of  >NH  into  0  takes  place  sometimes 
by  the  action  of  water  at  ordinary  temperatures,  and  also  on 
heating  with  dilute  acid.  The  imido-ethers  (action  of  alcohols 
on  nitriles)  are  decomposed  very  easily  : 


HCO.OC2H5 

Ethyl-imido-fonnate.  Ethyl  formate. 

The  nitriles  may  be  converted  into  esters  of  the  acids  through 
the  means  of  imido-ethers.  Benzoyl-formic  ester  is  easily 
prepared  by  passing  hydrochloric  acid  into  a  cold  solution  of 
benzoyl  cyanide,  C6H5.CO.CN,  in  alcohol.  The  liquid  is  allowed 
to  stand  for  several  days,  and  the  ester  is  separated  with  water. 
The  conversion  of  guanidine  into  urea  by  the  action  of  boiling 
baryta-  water  is  another  example  of  the  change  of  NH  into  0. 

The  transformation  of  N  =  N  into  H  and  OH  is  brought  about 
by  prolonged  boiling  with  water  of  the  esters  of  the  diazo  acids 

N 
/ 

of  the  paraffin  series.    The  ester  of  diazo-acetic  acid,  HC\  , 

N 


gives  the  ester  of  gly  collie  acid. 


f 
C0 


OXIDATION.  45 

C.  Conversion  of  the  Sulphonic  Acid   Group  into  the 
Hydroxyl   Group.1 

This  reaction,  which  is  often  employed  in  the  aromatic 
series,  is  brought  about  by  the  fusion  of  the  sulphonic  acids 
with  caustic  potash,  followed  by  decomposition  by  an  acid  : 

C6H5.S02.OK  +  2KOH = C6H5.OK + K2S03  +  H20. 

The  sulphonic  acid  is  heated  in  a  silver  or  nickel  crucible  by 
vapor  of  naphthalene  or  anthracene  with  solid  caustic  potash 
to  which  is  added  a  little  water.  The  time  of  the  fusion  varies 
from  several  minutes  to  several  hours,  and  the  temperature 
varies  from  160°  to  300°  C.  The  yield  of  the  phenol  increases 
with  the  temperature  and  the  amount  of  alkali.  With  6  mole- 
cules of  KOH  on  C6H5.S02.OK  and  heating  for  1  hour,  a  yield 
of  94  per  cent,  of  the  theoretical  may  be  obtained.  The  exact 
time  of  stopping  the  fusion  cannot  always  be  easily  recognized. 
When  the  reaction  is  finished,  the  mass  is  broken  up  and  dis- 
solved in  water  and  acidulated;  if  nothing  separates  out, 
•extract  with  ether. 

Instead  of  using  the  free  sulphonic  acid,  the  lead  salt  may 
be  employed,  which  is  often  prepared  in  order  to  purify  the 
acid.  When  an  aromatic  body  is  fused  with  potash  in  the 
presence  of  an  oxidizing  body,  there  may  occur  the  oxidation 
of  a  hydrogen  in  the  nucleus.  In  this  manner  the  hydroxy- 
anthraquinones  (alizarins)  may  be  prepared. 

If  there  are  two  sulphonic  acid  groups  in  the  same  molecule, 
by  using  suitable  precautions  a  single  one  may  be  substituted; 
if  the  reaction  is  very  energetic,  both  will  be  attacked: 


0  H  /(I)  S02.OH 
Uil4\(3)  S02.OH' 

Benzene-disulphonic  acid. 


1  This  is  equivalent  to  the  replacement  of  H  by  OH  through  the  medium 
of  the  sulphonic  acid  derivatives. 


46  ORGANIC  SYNTHESES. 

at  170-180°  .0.,  is  converted  into 

r  TT  /(I)  S02.OH 

UM4\(3)  OH 

Phenol-sulphonic  acid. 

Frequently  fusions  with  potash  lead  10  molecular  trans- 
positions. With  the  acid 

(para-phenol-sulphonic  acid), 

OTT 
resorcinol,  CeH^  /i^  QTT,  is  obtained,  which  is  a  meta-product. 

This  peculiarity  may  be  explained  by  two  successive  reac- 
tions, oxidation  and  reduction  (see  above). 

The  CH3  group  is  sometimes  oxidized  by  fusion  with  potash: 

r  H  (1)  CH3  .         p  R  /(I)  CO.OH 

V^6*l4/o\  Grk     nTT       gives       U6-tl4\    /0\    /^TT 
(Z)  ovJ2.U±l  \\^)  v/Xl 

Ortho-toluene-sulphonic  acid.  Ortho-oxybenzoic  acid. 

Soda  may  be  used  instead  of  potash;  but,  as  its  action  is  not 
so  energetic,  it  is  necessary  to  prolong  the  time  of  fusion  at  a 
higher  temperature. 

D.  Displacement  of  Sulphur  by  Oxygen. 

This  substitution  (exchange  of  two  valences  of  the  carbon 
atom)  is  readily  effected  by  the  oxides  or  salts  of  the  heavy  metals 
(PbO,  HgO,  AgN03,  ammoniacal  solution  of  a  silver  salt,  etc.), 
and  sometimes  also  by  alkalies.  Thus,  thiophenyl-urea  gives 
phenyl-urea, 

'NH2  m/NH2 

,NH.C6H5  ^XNH.CeHs' 

by  boiling  the  aqueous  or  alcoholic  solution  with  PbO,  or  freshly 
precipitated  HgO. 

With  silver  nitrate,  the  reaction  is  not  always  complete, 
intermediate  compounds  being  formed.  With  allyl-thio-urea, 


OXIDATION.  47 

for  instance,  there  is  first  formed  C^x^i^G  H  .AgN03,  which, 
on    moderately    heating    with    AgN03,  is    decomposed   into 

+Ag2S+2HN°3;    this  being   kept    neutral  by 


adding  baryta-water  from  time  to  time. 

The  dithionic  acids,  like  C6H5.CS.SH,  lose  S  on  boiling  with 
an  alcoholic  solution  of  potash. 

Oxidations  which  take  place  with  the  fixation  of  water  will 
be  taken  up  under  Chapter  V. 


CHAPTER  II. 

REDUCTION. 
I.  GENERAL  CONSIDERATIONS. 

REDUCTION  is  the  opposite  of  oxidation.    It  may  occur  in 
several  different  forms : 

(1)  Reduction  of  hydroxyl  oxygen,  as, 

C6H5.OH  +  H2  =  C6H5.H  +  H20. 

Phenol.  Benzene. 

(2)  Reduction  of  ketonic  oxygen  to  hydroxyl: 

CH3.CH :  0  +  H2  =  CH3.CH2.OH. 

Aldehyde.  AlcohoL 

(3)  Reduction  of  unsaturated  groups: 

CH2 

II       +H2= 
CH2 

Ethylene.  Ethane. 

CH3.C :  N  +  2H2  =  CH3.CH2.NH2. 

Methyl  cyanide.  Ethylamine. 

(4)  Reduction  of  halogen  compounds: 

CH2(C1)  .CO.OH  +  H2  =  CH3.CO.OH  +  HC1. 

Chlor-acetic  acid.  Acetic  acid. 

(5)  Reduction  of  nitro  derivatives: 

C6H5.N02  +  3H2 = C6H5.NH2  +  2H20. 

Nitrobenzene.  Aniline 

C6H5.NX  C6H5NH 

|  >0+2H2=  |     +H20. 

C6H5.N/  C6H5NH 

Azoxyoenzene.  Hydrazobenzene. 

48 


REDUCTION.  49 

(6)  Reduction  attended  by  a  decomposition  of  the  molecule:, 
thus,  the  phenylhydrazine   compound  of  acetaldehyde,  when 
reduced  with  sodium  amalgam,  gives  rise  to  two  separate  amines, 
aniline  and  ethylamine : 

CH3.CH  =  N.NH.C6H5  +  2H2  =  C6H5NH2 + CH3.CH2.NH2. 

II.  ACTION  OF  REDUCING  AGENTS. 

Though  the  most  logical  reagent  for  reduction  purposes 
would  be  hydrogen  in  its  nascent  condition,  yet  it  does  not 
appear  to  have  met  with  success  as  a  reducing  agent  for  organic 
compounds.  Attempts  have  been  made,  however,  to  employ 
clectrolytically  prepared  nascent  hydrogen,  but  the  results  have 
not  been  gratifying.  By  using  this  means,  Haussermann,1  in  act- 
ing on  nitrobenzene  dissolved  in  alcoholic  caustic  soda,  obtained 
hydrazo-benzene  and  benzidine  sulphate;  aniline  was  only  pro- 
duced when  a  cathode  of  zinc,  instead  of  platinum,  was  used. 

The  majority  of  reactions  involving  the  reduction  of  organic 
compounds  take  place  indirectly  through  the  use  of  various 
reducing  agents,  of  which  the  following  are  the  most  important : 

Hydriodic  acid  is  probably  the  strongest  reducing  agent 
employed  in  connection  with  organic  compounds.  Its  action 
depends  on  the  readiness  with  which  it  decomposes  into  free 
iodine  and  hydrogen;  it  may  be  employed  dissolved  either  in 
water  or  in  acetic  acid.  According  to  Berthelot,  who  was  the 
first  to  recognize  its  reducing  action  on  organic  substances, 
hydriodic  acid  is  capable  of  reducing  every  organic  compound 
to  the  limit  hydrocarbon  containing  the  same  number  of  carbon 
atoms.  He  recommended  heating  the  substance  to  be  reduced 
with  a  large  excess  of  hydriodic  acid  in  a  sealed  tube  for  several 
hours  at  a  temperature  of  275°  C.  The  action  of  hydriodic  acid 
may  be  considerably  accelerated  by  the  addition  of  phosphorus,2 

1  Chem.  Zeit.,  1893,  p.  129. 

2  The  increased  efficiency  of  the  hydriodic  acid  due  to  the  addition  of  phos- 
phorus may  be  accounted  for  by  the  fact  that  the  phosphorus  combines  with 
the  free  iodine  liberated  in  the  reduction  to  form  phosphorus  iodide;    and  the 


50  ORGANIC  SYNTHESES. 

which  also  has  the  advantage  of  preventing  the  formation  of 
undesirable  by-products.  It  is  probable  that,  in  the  reaction 
between  phosphorus  and  hydriodic  acid,  phosphonium  iodide  is 
formed  as  an  intermediate  step  in  the  reduction.  By  the  use 
of  phosphorus  and  hydriodic  acid,  it  is  possible  to  carry  out  a 
large  number  of  reductions  without  the  necessity  of  heating  in 
a  sealed  tube,  simply  boiling  the  compound  to  be  reduced  with 
strong  hydriodic  acid  in  a  flask  connected  with  an  inverted 
condenser  and  adding  fragments  of  phosphorus  from  time  ta 
time.1  For  some  reductions  yellow  phosphorus  is  required^ 
while,  for  others,  red  phosphorus  may  be  used.  In  cases  where 
very  energetic  reduction  is  necessary,  however,  recourse  must 
be  had  to  the  method  of  heating  the  mixture  in  a  sealed  tube 
to  a  high  temperature,  and  with  a  large  excess  of  hydriodicr 
acid.2 

Sodium  and  sodium  amalgam  are  largely  employed  as 
reducing  agents,  as  they  are  very  efficient  and  may  be  applied 
conveniently.  Sodium  is  mostly  used  in  connection  with  an 
alcoholic  solution  of  the  substance  to  be  reduced,  though,  at 
times,  either  water  or  ether  may  be  employed  as  the  solvent. 
There  appears  to  be  a  considerable  difference  in  the  action  of 
sodium  as  a  reducing  agent,  depending  on  the  nature  of  the 
alcohol  employed  as  the  solvent;  when  amyl  alcohol,  for  in- 
stance, is  used  as  the  medium,  the  reducing  power  of  the  sodium 
appears  to  be  greater  than  with  ethyl  or  methyl  alcohols. 
Sodium  amalgam  is  less  energetic  in  its  action  than  sodium.  An 

latter  in  the  presence  of  water  (also  generally  present  as  a  by-product  in  the  reduc- 
tion) further  reacts  to  give  hydriodic  and  phosphorous  acids.  So,  in  reality,  by 
the  intervention  of  the  phosphorus,  the  iodine  is  used  over  and  over  again  to 
effect  the  reduction;  while  at  the  same  time  the  phosphorus  also  removes  the 
water,  the  presence  of  which  would  soon  limit  the  reaction,  or  cause  the  forma- 
tion of  secondary  products: 

PI3+  3H2O=  3HI+  HgPOg. 

1  In  this  manner  iodoform,  CHI3,  may  be  reduced  to  methylene  iodide,  CH.jIa 
(see  Baeyer,  Berichte,  vol.  v,  p.  1095). 

2  By  employing  this  method  of  reduction,  anthracene,  CI4H10,  may  be  reduced 
to  the  hydrocarbon  C,4HM.     (See  Lucas,  Berichte,  vol.  xxi,  p.  2510). 


REDUCTION.  51 

amalgam  containing  about  2J-  per  cent,  of  sodium  is  generally 
employed,  as  this  is  solid  and  may  be  readily  pulverized.  Sodium 
amalgam  is  most  efficient  when  used  in  the  presence  of  carbon 
dioxide,  and  it  may  be  employed  in  alcoholic,  ethereal,  or 
acetic  acid  solutions.  As  sodium  hydrate  is  formed  in  the 
course  of  the  reaction  with  sodium  amalgam,  the  efficiency  and 
speed  of  the  reduction  may  be  increased  by  neutralizing  the 
alkali  with  acids. 

Metallic  tin  and  stannous  chloride  are  also  employed  exten- 
sively as  reducing  agents.  Tin  itself  is  principally  used  in 
connection  with  hydrochloric  acid,  and  the  metal  is  afterwards 
removed  by  precipitation  with  hydrogen  sulphide.  Stannous 
chloride  is  used  in  acid  solution,  and,  as  it  is  soluble  in  alcohol, 
it  may  be  conveniently  employed  with  this  solvent;  it  may  also 
be  used  with  glacial  acetic  acid.  Sometimes  an  alkaline  solu- 
tion of  tin  (sodium  stannite)  is  employed  for  reductions.  This 
solution  is  best  prepared  by  adding  powdered  stannous  chloride 
to  a  strong  solution  of  sodium  hydrate  until  a  precipitate  begins 
to  form. 

Zinc  may  be  employed  for  the  reduction  of  organic  com- 
pounds in  either  acid  or  alkaline  solutions,  and  at  times  even 
in  neutral  solution.  Zinc  dust  when  used  at  high  temperatures 
is  a  powerful  reducing  agent;  even  when  boiled  with  water, 
zinc  dust  is  capable  of  reducing  many  substances. 


III.  SUBSTITUTION  OF  HYDROGEN  FOR  HYDROXYL  OR 
OTHER  ELEMENT,  GROUP,  OR  RADICAL. 

A.  Reduction  of  Hydroxyl  and  Ketonic  Compounds. 

(i)  Reduction  of  Acids. — In  certain  cases  acids  are  converted 
into  aldehydes  by  displacing  the  OH  group  with  H.  Benzoic 
and  oxy-benzoic  acids  behave  in  this  manner.  The  first,  on 
treatment  with  sodium  amalgam  in  the  presence  of  water, 
gives  benzaldehyde;  but  the  second  one  is  converted  into  the 
corresponding  alcohol.  The  indirect  method  which  would  lead 


5 2  ORGANIC  SYNTHESES. 

to  the  same  result  consists  in  heating  the  salt  of  the  acid  with 
a  formate,  or  in  reducing  the  chlorides  or  anhydrides  of  the 
acids.  In  the  latter  case,  by  an  energetic  reduction,  the  corre- 
sponding alcohols  may  be  obtained.1  The  reduction  of  succinyl 
chloride,  however,  with  sodium  amalgam  and  acetic  acid,  does 
not  appear  to  give  the  corresponding  aldehyde,  but  the  lac  tone 
of  ^-oxy butyric  acid.  Phthalyl  chloride  behaves  in  the  same 
manner.  Under  the  influence  of  more  energetic  agents,  such 
as  hydriodic  acid,  acids  are  converted  into  hydrocarbons  by 
conversion  of  the  CO. OH  group  into  CH3.  Thus,  stearic  acid, 
Ci8H3602,  gives  a  hydrocarbon,  Ci8H38,  and  benzoic  acid, 
C7H602,  gives  toluene,  C7H8. 

According  to  Berthelot,  reduction  by  means  of  hydriodic 
acid  takes  place  in  the  following  manner :  The  acid  to  be  reduced 
is  heated  on  an  oil-bath  to  200-280°  C.with  20  to  30,  or  even 
100  times  its  weight  of  hydriodic  acid  (sp.  gr.  =  1.8  to  2). 
The  tubes  are  opened  from  time  to  time  in  order  to  allow  of 
the  escape  of  gas,  which  may  be  collected  over  mercury  when 
it  is  desired  to  analyze  it.  On  account  of  the  great  pressure 
which  exists  in  the  tubes,  they  must  be  opened  in  a  very  careful 
manner.  The  reduction  of  the  fatty  acids,  and  of  products 
obtained  by  the  action  of  phosphorus  pentachloride  on  ketones, 
according  to  Kraft,  takes  place  in  the  following  manner:  In 
each  tube  there  is  placed  2  to  4  grams  of  the  acid,  together 
with  2  to  4  times  the  quantity  of  hydriodic  acid  (sp.  gr.  =  1.7) 
and  J  part  of  red  phosphorus;  the  tubes  are  heated  for  3  to  5 
hours  at  210-240°  C.,  after  which  they  are  opened.  A  small 
amount  of  phosphorus  is  added,  and  the  tubes  are  reheated  to- 
210-210°  C.  These  operations  are  repeated  two  or  three 
times,  and  finally  water  is  added  to  decompose  the  iodide  of 
phosphorus  which  is  formed.  The  hydrocarbons  are  distilled 
in  steam,  and  then  heated  with  a  solution  of  caustic  alkali. 

But  little  is  known  concerning  the  reduction  of  acid  amides 
and  imides.  Sodium  amalgam  with  acetamide  gives  a  small 

1  See  Zaytzeff,  A  New  Method  for  the  Conversion  of  Aliphatic  Acids  into  the 
Corresponding  Alcohols,  Kagan,  1870  (in  Russian). 


REDUCTION.  53, 

quantity  of  alcohol.    The  action  of  sodium  in  amyl  alcohol  on 
phthalimide  reduces  the  two  CO  groups: 

CH2.NH2 


(2)  Reduction  of  Aldehydes.  —  Aldehydes  are  converted  into 
alcohols  by  the  action  of  sodium  amalgam  in  an  acidulated 
(H2S04)  aqueous  solution;   the  alcohol  so  formed  is  separated 
by  distillation,  the  distillate  being  further  treated  with  potas- 
sium carbonate.    The  higher  aldehydes  of  the  aliphatic  series, 
which  are  difficultly  soluble  in  water,  are  reduced  by  the  use 
of  zinc  dust  in  glacial  acetic  acid  solution;  in  this  case,  however, 
the  reaction  results,  not  in  the  formation  of  the  alcohol,  but  of 
the  corresponding  acetic  ester,  which  must  be  saponified  in 
order  to  obtain  the  alcohol. 

Derivatives  of  chlor-substituted  aldehydes,  such  as  chloral, 
are  reduced  to  the  corresponding  alcohols  by  zinc  ethyl;  thusr 
chloral  gives  tri-chlor-alcohol.  In  order  to  reduce  aromatic 
aldehydes  it  is  necessary  to  suspend  them  in  water  or  dissolve 
them  in  dilute  alcohol.1  For  the  reduction,  an  alcoholic  solu- 
tion of  potash  may  be  used: 

2C6H5.CHO  +  KHO  =  C6H5.CH2.OH  +  C6H5CO.OK. 

The  aromatic  aldehydes  are  also  converted  into  amines  by 
the  action  of  ammonium  formate;  for  example,  the  conversion 
of  benzaldehyde,  C6H5.CHO,  into  benzylamine,  C6H3.CH2.NH2. 
By  the  prolonged  action  at  130°-150°  C.  of  a  concentrated 
solution  of  hydriodic  acid  and  red  phosphorus,  aldehydes  are 
converted  into  hydrocarbons  (substitution  of  CHO  by  €H3)  : 

C6H5CHO  -  •-»  C6H5CH3.2 

(3)  Reduction  of  Ketones  and   Quinones.  —  The  conversion 
of  the  CO  group  into  CH.OH  or  C.OH,  and  the  production  of 

1  The  aromatic  aldehydes  are  liable  to  form  condensation  products. 

2  For  the  action  of  halogen  acids  on  methylene  oxide,  see  Jour.  Soc. 
Chim.  Russe,  vol.  19,  p.  169. 


54  ORGANIC  SYNTHESES. 

alcohols  and  phenols  by  the  aid  of  ketones  and  quinones,  takes 
place  by  the  action  of  sodium,  or  its  amalgam  in  the  presence 
of  water,  by  boiling  with  a  solution  of  alcoholic  potash  in  the 
presence  of  zinc  powder,  and  even  by  the  action  of  sulphurous 
acid.  Quinone,  CeHiC^,  is  readily  converted  into  hydroqui- 
none;  so  much  so,  in  fact,  that,  in  an  alcoholic  solution  under 
the  influence  of  sunlight,  the  quinone  changes  the  alcohol  into 
aldehyde. 

The  ketone,  dissolved  in  ether  or  benzene,  is  placed  in  a 
flask  with  water;  there  is  then  added  small  shavings  of  metallic 
sodium,  which  maintain  themselves  between  the  two  liquids. 
It  is  usually  necessary  to  moderate  the  energy  of  the  reaction 
by  cooling.  When  the  odor  of  the  ketone  has  disappeared,  the 
upper  layer  of  liquid  is  removed,  and  the  alcohol  produced 
is  isolated  by  crystallization  or  distillation.  There  are  also 
formed  condensation  products. 

The  ke tonic  acids  behave  like  the  ketones;  thus,  pyruvic 
acid  gives  lactic  acid  with  sodium  amalgam  in  the  presence  of 
water : 

CH3.CO.CO.OH  +  H2  =  CH3.CH(OH)  .CO.OH. 

In  order  to  avoid  the  decomposition  of  certain  ketonic  acids 
by  the  alkali,  it  is  necessary  to  keep  the  temperature  from 
rising  too  high,  and  to  neutralize  from  time  to  time  with  an 
acid.  In  certain  cases,  by  the  reduction  of  ketonic  acids, 
there  are  formed  lac  tones  in  place  of  oxyacids;  and  some- 
times the  latter,  which  may  be  formed  at  first,  are  reduced 
in  their  turn.  For  instance,  benzophenone-meta-carboxylic 
acid,  C6H5.CO.C6H4.CO.OH,  with  sodium  amalgam,  is  con- 
verted into  benzo-hydroxy-meta-carboxylic  acid : 

C6H5.CH(OH).C6H4.COOH,  and  C6H5.CH2.C6H4.CO.OH. 

The  conversion  of  the  CO  group  into  CH2,  and  the  formation 
of  hydrocarbons  with  the  aid  of  ketones,  is  brought  about  by 
the  action  of  hydriodic  acid  under  the  same  conditions  as  for 


REDUCTION.  55 

aldehydes,  or  by  distillation  with  zinc  dust.    Thus,  benzophc- 
none,  (C6H5)2CO,  gives  diphenylme  thane,  (Cel^.CHo.1 

(4)  Reduction  of  Alcohols.  —  The  reduction  of  alcohols  (con- 
version of  OH  into  H)  usually  takes  place  in  an  indirect 
manner.  The  reduction  of  phenols  (such  as  the  conversion  of 
phenol,  C6H5OH,  or  of  pyrogallol,  C6H3(OH)3,  into  C6H6)  is 
brought  about  by  distillation  with  zinc  dust  or  with  phosphorus 
pentasulphide.  Oxypyridine  and  quinoline  are  also  reduced 

with  zinc  dust.    Cuminic  alcohol,  C6H4/  ^^2'  on  dis" 


tillation  with  zinc  dust,  gives  cymene,  C6H4<^  CH2.CH2.CH3. 

Certain  reductions  of  aromatic  alcohols  are  accompanied  by 
an  oxidation  :  benzyl  alcohol,  with  alcoholic  potash,  gives  toluene 
and  benzoic  acid.  The  simple  ethers  of  aromatic  alcohols  are 
separated  by  heat  into  aldehydes  and  hydrocarbons;  benzyl 
ether  gives  benzaldehyde  and  toluene  : 


C6H6.CHO. 


Hydriodic  acid  and  red  phosphorus,  on  heating,  furnish  a 
good  means  of  reduction  for  alcohols  of  the  paraffin  series,  as 
well  as  those  of  the  aromatic  series  having  the  OH  in  a  side 
chain,  and  also  oxy  acids.  Aromatic  lac  tones  or  phthaleins 
are  also  reduced  with  zinc  powder  in  alkaline  solution,  and 
yield  phthalines.  Ethylene  oxide  is  readily  converted  into 
alcohol  with  sodium  amalgam: 


2V  CH2.OH. 

I   >+H2=j 

CH/  CH3 

This  reaction  may  be  considered  as  a  reduction  followed  by 
a  fixation   of  water.    The   reverse   reaction  —  reduction   with 

1  The  keto-phenone,  C6H6CO-CH3,  treated  with  hydriodic  acid,  does  not  give 
ethyl-benzene,  CJHgCgHi,  but  condensation  products. 


56  ORGANIC  SYNTHESES. 

elimination  of  water — is  effected  by  boiling  polyatomic  alcohols 
with  formic  acid.  There  is  at  first  formed  a  monoformin, 
which  is  decomposed  with  liberation  of  water  and  carbon 
dioxide;  it  is  in  this  manner  that  allyl  alcohol  is  prepared  from 
glycerin. 

Ketonic  aldehydes,  with  zinc  dust  in  acetic  acid  solution, 
suffer  reduction  of  their  hydroxyl  group,  but  in  alkaline  solu- 
tion the  CO  group  is  reduced.  For  example,  benzoin,  in  the 
first  case,  is  transformed  into  desoxybenzoin,1  and,  in  the  second 
case,  into  hy droxy benzoin : 

CO.C6H5  CO.C6H5         HO.CH.C6H5 

I  >    I  or 

HO.CH.C6H5  CH2.C6H5        HO.CH.C6H5 

B.  Substitution  of  Other  Groups  by  Hydrogen. 

(i)  Substitution  of  the  Halogens. — This  substitution  is  brought 
about  by  the  action  of  a  large  number  of  reducing  agents :  sodium 
amalgam  in  the  presence  of  water,  metals  in  the  presence  of 
acids,  zinc  dust  with  alkali,  hydriodic  acid  alone  or  in  the 
presence  of  red  phosphorus.  The  last  reagent  is  very  ener- 
getic. Thus,  C8Hi7.C(Cl2).CH3,  heated  in  a  sealed  tube  with 
this  mixture,  is  completely  converted  into  decane,  Ci0H22.  In 
order  to  substitute  iodine  with  hydrogen,  the  zinc-copper 
couple  may  be  used  with  advantage.  This  is,  in  fact,  the  best 
means  of  preparing  methane:  into  a  vessel  furnished  with  a 
zinc-copper  couple  there  is  led  an  alcoholic  solution  of  methyl 
iodide.  The  flask  is  then  closed  with  a  cork  furnished  with  an 
escape-tube,  and  heated  gently  on  a  water-bath.  The  gas  is 
given  off,  and,  by  properly  regulating  the  temperature,  a  slow 

1  Desoxybenzoin  (phenyl-benzyl-ketone),  with  reducing  agents,  furnishes 
partly  the  corresponding  pinacone  and  partly  the  secondary  alcohol,  which,  under 
the  influence  of  acetic  acid,  loses  a  molecule  of  water  and  gives  the  hydrocarbon: 

C6H5.C-OH                    C6H5.CH-OH  C6H,-CH 

2           I >               \  +  ||    . 

C6H5  •  CHj                       C6H5  •  CH2  C6Hj  •  CH 
Pinacone.                              Alcohol. 


REDUCTION.  57 

and  regular  current  may  be  obtained  containing  only  a  small 
quantity  of  the  vapors  of  alcohol  and  methyl  iodide.  Two 
c.c.  of  CH3I  give  700  c.c.  of  CH4.  The  reaction  may  be  ex- 
pressed as  follows  : 

CH3I  +  Zn  +  H20  =  Zn/       +  CH4. 


In  order  to  replace  halogens  in  an  aromatic  nucleus,  it  is 
necessary  to  use  sodium  amalgam  in  the  presence  of  water,  or 
hydriodic  acid  with  phosphorus  in  sealed  tubes.  Metals  with 
acids  react  but  seldom  and  very  slowly;  while,  on  the  contrary, 
the  halogens  in  side-chains  are  displaced  very  easily.  Chlorine 
in  the  pyridine  nucleus  is  removed  by  tin  and  hydrochloric 
acid: 

C5H3N(C1).CO.OH  ---  >  CsHtN.CO.OH. 

Chlor-nicotinic  acid.  Nicotinic  acid. 

Also,  in  the  chlorides  of  organic  acids,  the  halogen  is  easily 
replaced.  The  chlorides  of  the  sulphonic  acids  behave  in  a 
similar  manner:  thus,  R.S02C1  is  converted  into  R.S02H. 
The  reduction  should  take  place  in  an  alkaline  solution;  in 
acid  solution  the  reduction  goes  still  further,  and  a  mercaptan 
is  formed,  R.SH.  Sometimes  the  reduction  is  accompanied  by 
a  decomposition  of  the  molecule;  chlor-sulphocymene,  CioH7, 
S02.C1,  with  sodium  amalgam,  gives  Ci0H8  and  S02. 

It  is  easy  to  remove  bromine  when  combined  with  oxygen 
in  derivatives,  as  in  phenol  bromide,  C6H5.OBr.  Tribrom- 

phenol-bromide,  CeB  ,  loses  bromine   on   boiling   with 


alcohol,  giving  tribrom-phenol, 

Several  halogen  atoms  may  be  replaced  successively  in 
the  combinations  in  which  they  occur.  In  compounds  of  the 
paraffin  series,  if  the  halogens  occur  with  neighboring  carbon 
atoms,  instead  of  a  simple  replacement  of  the  halogen,  there  is 
generally  a  rupture  of  the  molecule,  with  the  formation  of 
unsaturated  compounds.  On  partial  reduction  with  hydriodic 


$8  ORGANIC  SYNTHESES. 

acid,  for  instance,  propylene  chloride,  CH3.CH(C1).CH2C1,  gives 
isopropyl  chloride,  CH3.CHC1.CH3,  and  propylene  bromide, 
CH3.CH(Br).CH2Br,  gives  isopropyl  bromide,  CH3.CHBr.CH3. 
The  compound,  CH3.CH(C1).CH2I,  treated  with  the  theoretical 
quantity  of  hydriodic  acid,  is  converted  into  isopropyl  chloride, 
CH3.CH.(C1).CH3;  with  an  excess,  there  is  formed  isopropyl 
iodide,  CH3.CH(I).CH3. 

(2)  Substitution  of  the  Nitrile  Radical  (CN).— (See  page  62.) 
<3)  Substitution  of  the  Nitro  Group  (N02).— (See  page  65.) 
By  the  use  of  diazo  compounds,  see  the  substitution  of 
-N:NRby  H. 

(4)  Substitution  of  the  Nitroso  Group  (NO). — This  is  brought 
.about  by  boiling  nitroso-compounds  with  concentrated  hydro- 
chloric acids.    Thus,  nitroso-dimethylaniline,  (CH3)2N.NO,  is 
converted  into  a  salt  of  dimethylaniline.    The  same  result  is 
obtained  by  using  a  solution  of  alcoholic  potash,  or  certain 
other  reducing  agents  (see  page  63). 

(5)  Substitution  of  the  Amido  Group  (NH2). — This  reaction  is 
rarely  produced  directly.    Ethylamine  at  275°  C.,  with  hydriodic 
,acid,  is  decomposed  according  to  the  equation : 

C2H5.NH2  +  SHI  =  C2H6  +  NHJ  + 12. 

Tor  the  use  of  the  azo  derivatives  in  effecting  this  reaction, 
see  the  substitution  of  N  :NR  by  H., 

(6)  Substitution    of     the    Diazo     Group    ( -  N :  NR) .— This 
:reaction   often   takes   place.     Into    an   acid   solution   of   the 
sulphate   or   nitrate  of  an  amine   a  slow  current  of  N203  is 
passed  (it  is  best  to  use  theoretical  quantities) .    The  salt  of  the 
diazo    derivative    which    is    formed    (diazo-benzene-sulphate, 
€6H5.N  :N.O.S02.OH,  for  example)  is  isolated  by  alcohol  and 
ether,  and  then  decomposed  by  boiling  with  absolute  alcohol, 
^according  to  the  equation: 

€6H5.N  :N.O.S02.OH+CH3.CH2.OH 


REDUCTION.  59^ 

The  separation  of  the  diazo-salt  may  be  dispensed  with; 
the  amido  compound  is  dissolved  in  a  mixture  of  concentrated- 
sulphuric  acid  and  alcohol;  there  is  then  added  the  theoretical 
quantity  of  a  concentrated  aqueous  solution  of  sodium  nitrite 
or  an  excess  of  ethyl  or  amyl  nitrite. 

The  diazo-chlorides  are  decomposed  in  the  same  manner 
by  means  of  stannous  chloride.  If  an  excess  of  stannous 
chloride  is  added  to  a  cold  dilute  solution  of  the  diazo-chloride 
(1  mol.  NaN02,  1  mol.  amine,  2  mols.  HC1),  the  following^ 
reaction  will  take  place : 

CnHtfN :  N.C1 + SnCl2 + H20 = CnHy+ 1  +  SnOCl2  +  HCI  +  N"2. 

In  this  reaction  there  are  probably  formed  some  hydrazines 
as  secondary  compounds.  Hydrazines  may  also  be  used  to 
replace  N:N.R  by  H,  for,  by  boiling  them  with  copper  sul- 
phate, they  are  decomposed  with  evolution  of  N2.  Thus, 
phenylhydrazine,  C6H5.NH.NH2,  gives  benzene,  C6H6.  In  cer- 
tain cases,  boiling  the  diazo  body  with  alcohol  causes  the 
N:N.R  to  be  replaced,  instead  of  by  H,  by  O.C2H5.  For 
instance,  while  the  ortho-diazo-benzoic  acid  sulphate, 

p  TT  /(I)  CO.OH 
U±±4\(2)N:N.HS04> 

gives  only  benzoic  acid  by  this  reaction,  the  para  and  meta 
isomers  yield,  besides  benzoic  acid,  meta-  and  para-ethoxy- 
benzoic  acids : 

p  H  /CO.OH 
UM4\OC2H5' 

In  place  of  the  diazo-salts,  the  diazo-amido  compounds 
(action  of  N203  on  an  alcoholic  solution  of  an  amido  derivative) 
may  be  decomposed  by  alcohol.  Thus: 

C6H5.N:  N.NH.C6H5+CH3.CH2.OH 

=  C6H6  +  C6H5.NH2 + N2 + CH3  .CH<X 


60  ORGANIC  SYNTHESES. 

In  this  reaction  half  of  the  amido  compound  is  reformed, 
but  this  may  be  avoided  by  treating  the  substance  with 
a  mixture  of  alcohol  and  nitrous  ether.  The  diazo-amido 
compound  obtained  is  decomposed  with  alcohol,  and  the  amido 
body  which  is  reformed  reacts  again  with  the  nitrous  ether. 

(7)  Substitution  of  the  Sulphonic  Acid  Group  (S03H).— This 
is  observed  in  the  case  of  ortho-amido-thiosulphonic  acid  of 
dimethylaniline : 

/(l)S.SOaH    H  /d)SH 

C6H3f-(2)NH2       -^~>    C6H3^(2)NH2 

\(4)  N(CH3)2  \(4)  N(CH3)2 

By  the  reduction  of  this  body,  a  mercaptan  is  formed. 

(8)  Substitution  of  Oxygen. — This  has  already  been  studied 
in  the  reduction  of  aldehydes,  ketones,  nitroso  derivatives,  and 
oxyazo  bodies.    The  reduction  of  the  latter  is  identical  with 
that  of  the  azo  derivatives. 

(9)  Substitution  of  Sulphur. — This  takes  place  by  the  action 
of  zinc  (or  of  zinc  dust)  and  hydrochloric  acid,  or  with  sodium 
amalgam.    C6H5.CS.NH2  is  converted  into  C6H5.CH2.NH2. 

(10)  The  Removal  of  Oxygen. — This  takes  place  very  rarely; 
in  general  it  is  the  replacing  of  OH  by  H.    As  an  example  of  the 
removal  of  oxygen  may  be  cited  the  conversion  of  the  sulphinic 
acids,  R.S02H,  into  mercaptans,  R.SH,  by  zinc  dust  and  dilute 
sulphuric  acid,  or  with  tin  and  hydrochloric  acid.    The  conver- 

C6H5.NX  C6H5.N 

sion  of  azoxy-benzene,  |  >0,  into  azo-benzene,  ||  , 

C6H5.N/  C6H5.N 

is  not  complete. 

IV.     FIXATION   OF   HYDROGEN. 

There  is  a  fixation  of  hydrogen  during  the  reduction  of 
unsaturated  compounds,  or,  in  general,  in  those  bodies  which 
have  several  elements  united  by  more  than  one  bond.  We 


REDUCTION.  6  1 

have  considered  the  reduction  of  aldehydes,  not  as  one  of  addi- 
tion of  H,  but  as  the  replacement  of  OH  by  H  in  the  dihydrates  : 

+  H2  =  H20  +  CH3.CH2.OH. 

Hydrocarbons,  like  ethylene  and  acetylene,  give  ethane  when 
heated  to  500°  C.  with  hydrogen;  at  the  ordinary  temperature, 
they  combine  with  hydrogen  in  the  presence  of  platinum  black. 
At  150°  C.  in  sealed  tubes,  the  phenyl  derivatives  of  the  unsatu- 
rated  hydrocarbons  fix  hydrogen  by  means  of  concentrated 
hydriodic  acid.  Thus: 

eHs  CH2.C6H5 


Tolane.  Diphenyl  -ethylene.  Dibenzyl. 

Hydriodic  acid  permits  of  the  addition  of  hydrogen  to  ben- 
zene and  its  numerous  derivatives,  and  there  may  thus  be  ob- 
tained, by  a  prolonged  reduction,  the  derivatives  of  benzene  hexa- 
hydride.  It  is  more  convenient  to  employ  absolute  ethyl  or 
&myl  alcohol  and  sodium.  In  this  way  may  be  prepared  piper- 
idine,  C5HiiN  =  C5H5N.H6,  from  pyridine.  Hydrogen  cannot 
be  added  to  the  unsaturated  alcohols  with  hydriodic  acid, 
because  the  iodides  are  formed;  in  this  case  the  reducing  agent 
should  be  sodium  amalgam,  or  zinc  with  an  acid  : 

CH2  :  CH.CH2OH  +  H2  =  CH3.CH2.CH2.OH 

Allyl  alcohol.  Propyl  alcohol. 

Iron  and  acetic  acid  appear  to  be  the  best  for  converting 
unsaturated  aldehydes  into  the  saturated.  Under  these  condi- 
tions, the  CHO  group  is  often  changed  into  CH2OH,  and  some- 
times more  readily  than  C  =  C  into  CH  —  OH.  Sodium  amalgam 
in  alkaline  solution  is  the  best  for  converting  the  unsaturated 
acids,  like  cinnamic  acid,  CeHsCH  :CH.COOH,  into  saturated 
acids,  like  C6H5.CH2.CH2.COOH.  Those  which  resist  this 
action,  like  crotonic  acid,  CH3.CH:CH.COOH,  are  reduced  with 
hydriodic  acid  and  red  phosphorus  at  160°  C.  At  130°  C.  there 


62  ORGANIC  SYNTHESES. 

is  a  fixation  of  hydriodic  acid;  the  iodo-derivative  then  reacts 
with  hydriodic  acid  again  with  the  splitting  off  of  2  atoms  of 
iodine. 

Reduction  causes  nitriles  to  pass  into  amines: 

R.CN+2H2=R.CH2.NH2, 

with  partial  hydrolysis  however;  besides  primary  amines, 
there  are  also  formed  secondary  and  tertiary  amines.1  This 
reduction  is  generally  effected  with  zinc  and  dilute  sulphuric 
or  hydrochloric  acid  in  aqueous,  alcoholic,  or  ethereal  solution. 
Sodium  in  absolute  alcohol  may  also  be  used.  In  this  case  the 
aromatic  nitriles  give  secondary  products,  as  the  reduction 
takes  place  partly  according  to  the  equation  : 

R.CN  +  H2=RH+CNH, 

with  the  formation  of  a  hydrocarbon  and  hydrocyanic  acidr 
and  as  the  amines  and  hydrocarbons  formed  also  submit  to  a 
further  fixation  of  hydrogen. 

The  pyrazols,  with  sodium  in  absolute  alcohol,  give  pyrazo- 
lines  and  diamines: 


| 
C 


CH2.CH2X  CH2-CH2.NH.C6H5 

N.C6H5->|  >N.CeH5-H 

H=N  CH  =  N  /  CH2.NH2 

Phenyl-pyrazol.  Phenyl-pyrazoline.  Phenyl-trimethylene-diamine. 


The  oximes  are  reduced  in  the  same  manner  to  amines,  and 
the  group  >C  =  N.OH  becomes  >CH.NH2.  In  this  manner 
it  is  possible  to  realise  the  synthesis  of  aspartic  acid  by  the 
reduction  of  the  oxime  obtained  by  the  action  of  hydroxylamine 
on  oxalo-acetic  ester.2 

The  azo  compounds,3  C6H5.N  =  N.C6H5,  are    readily    con- 

1  See  Gaz.   chim.  Ital.,  vol.   9,   p.   555. 
Ubid.,  vol.  17,  p.  519. 

3  Acid  reducing  agents,  like  stannous  chloride  in  the  presence  of  sulphuric, 
acid,  convert  the  azo  bodies  into  diamines. 


REDUCTION.  63; 

verted  into  hydrazo  bodies,  C6H5.NH— NH.C6H5,  by  sodium 
amalgam  in  alcoholic  solution,  zinc  powder,  or  ammonium 
sulphide.  To  use  the  latter,  the  compound  is  dissolved  in 
alcohol,  saturated  with  ammonia,  then  treated  with  a  current  of 
hydrogen  sulphide.  The  sulphur  is  separated  by  filtration; 
and  on  the  addition  of  water,  the  hydrazo  body  is  precipitated. 
The  azo  bodies  may  also  be  reduced  with  ferrous  sulphate  in 
alkaline  solution.  It  is  sufficient  to  add  the  ferrous  sulphate 
to  an  alkaline  solution  of  the  compound  until  the  precipitation  of 
ferric  hydrate  ceases.  Acid  reducing  agents,  such  as  stannous 
chloride  in  the  presence  of  sulphuric  acid,  convert  azo  bodies 
into  diamines.  The  diazo  compounds  are  converted  into- 
hydrazines  by  reducing  agents  like  SnCl2  in  HC1 : 

C6H6.N :  N.C1  +  2H2  =  C6H5.NH.NH2 

Diazo-benzene  chloride.  Phenyl-hydrazine. 

The  hydrazines  are  decomposed  by  the  fixation  of  hydrogen.1 

V.  REDUCTION   OF   NITRO   AND   NITRO   COMPOUNDS. 

Nitroso  derivatives  are  converted  into  amines  when  the 
oxygen  of  the  NO  group  is  replaced  by  H2.  This  reduction 
is  generally  brought  about  by  zinc  and  acetic  acid,  or  with  tin 
and  hydrochloric  acid. 

The  reduction  of  nitrosamines  furnishes  a  method  for  the 
preparation  of  secondary  hydrazines : 

CHa\*T™  ^\N.NH2 


Nitroso-dimethyl-  Methyl-phenyl- 

phenyl-amine.  hydrazine. 

In  certain  cases  the  reaction  may  proceed  in  another  manner; 
thus,  with  the  preceding  body,  it  may  be : 


1  The  hydrazines  are  bodies  derived  theoretically  from  diamidogene, 
by  substitution  of  paraffin  or  aromatic  radicals  (or  alcoholic,  phenolic,  or  acidio 
radicals) ,  for  one  or  several  atoms  of  hydrogen.  There  are  primary,  secondary,, 
tertiary,  and  quaternary  hydrazines. 


^4  ORGANIC  SYNTHESES. 

The  reduction  of  nitroso-anilides  proceeds  exclusively  in  this 
manner,  with  the  evolution  of  ammonia  and  the  formation  of 
anilides  : 


When  isonitroso  bodies  are  reduced,  there  is  a  complication 
of  the  molecule.  For  the  reduction  of  oximes,  see  p.  62. 

It  is  well  known  that  reduction  converts  N02  into  NH2; 
the  process  of  Zinin  for  obtaining  aromatic-amido  compounds 
depends  on  this  reaction.  In  the  paraffin  series  the  reduction 
of  N02  (nitro-e  thane,  for  example)  to  NH2  is  probably  not  at 
all  analogous  to  that  which  takes  place  in  the  aromatic  series.1 
The  agents  mostly  employed  for  the  reduction  of  nitro  com- 
pounds are  tin  and  hydrochloric  acid,  and  a  solution  of  stannous 
chloride  in  hydrochloric  acid.  The  advantage  of  these  bodies 
is  the  ease  of  separating  the  tin  by  sulphuretted  hydrogen;  in 
the  solution  there  remains  only  the  chloride  of  the  amido  com- 
pounds. The  amines  with  a  basic  character  are  precipitated 
from  their  acid  solutions  with  ammonia;  amido-phenols,  by 
sodium  carbonate;  amido-carboxylic  acids,  by  sodium  acetate. 
The  reduction  sometimes  proceeds  in  an  abnormal  manner; 

//I  \    pTT 

thus  ortho-nitro-toluene,  C6H4<^  \2  -^^  ,  with  tin  and  hydro- 


XI)  CH3 

chloric  acid,  gives  para-chlor-ortho-toluidine,  C6H3^—  (2)  NH2; 

\4)C1    ' 

«-brom-/?-nitro-  naphthalene,  CioH6<^-^Q  ,  with  the  same  reduc- 

ing agent  gives  /?-naphthylamine,  CioH7.NH2.    In  such  cases, 
the   tin  is  replaced  by  iron   or   zinc   dust   and   acetic   acid; 

there  will  then  be  obtained  brom-naphthylamine,  Cio 
the  normal  derivative  of  brom-nitronaphthalene,  Ci0 


1  Bull.  Soc.  Chim.,  vol.  46,  p.  266. 


REDUCTION.  65 

By  a  very  energetic  reduction  N02  may  be  replaced  by  H; 
thus,  by  using  a  large  excess  of  iron  and  acetic  acid,  nitro- 
benzene, C6H5.N02,  gives  benzene,  C6H6,  and  ammonia;  and 

trinitro-mesitylene,  Ce^(NO$  J,  Sives  a  cumidine, 

When  the  compound  contains  several  N02  groups,  it  is 
easily  possible  to  reduce  one  after  another  by  means  of  sulphu- 
retted hydrogen,  and  in  the  order  that  is  desired.  For  example : 

/(I)  CH3 
dinitro-toluene,  CoH^-(2)  N02,  with  sulphuretted  hydrogen 

\4)  N02 
In  alkaline  solution,  cold,  gives  only  ortho-nitro-para-toluidine, 

XI)  CH3 

CeH3^— (2)  N02;  if  heat  is  employed,  its  isomer  is  obtained, 
\(4)  NH2 

/(I)  CH3 
€6H3^-(2)  NH2;  if  tin  and  hydrochloric  acid  in  alcoholic  solu- 

\4)  N02 
tion  are  used,  the  latter  body  only  is  obtained. 

Sometimes  in  reductions  there  occurs  an  evolution  of  C02. 

•  XI)  COOH 

Thus,    dinitrobenzoic     acid,    C6H3^-(2)  N02    ,    gives    meta- 

\(4)  N02 

phenylene-diamine,  C6H4<^  Lc  ^H^      Brom-nitrobenzoic  acid, 

/(I)  COOH  /(2)Br 

€6H3^-(2)  Br       ,    gives    meta-brom-aniline,    C6H4<(  >,c  MTT  . 

\(4)  N02 

Hence  it  is  necessary  to  take  particular  precautions  in  the  reduc- 
tion of  nitro-carboxyl  acids.  The  favorite  method  is  to  dissolve 
them  in  aqueous  ammonia  or  in  baryta-water,  and  to  add 
ferrous  sulphate  in  a  very  concentrated  solution. 

The  reduction  of  nitro-nitriles  is  surrounded  with  difficulties. 
Sulphuretted  hydrogen  cannot  be  employed,  as  it  is  liable  to 
form  a  compound  with  the  nitrile;  other  reducing  agents  cause 
a  saponification.  The  best  method,  in  certain  cases,  is  to  treat 
the  derivative  with  tin  and  glacial  acetic  acid  saturated  with 
hydrochloric  acid. 


66  ORGANIC  SYNTHESES. 

Nitro  derivatives  are  sometimes  reduced  in  a  complicated 
manner. 

VI.  REDUCTION   WITH  DECOMPOSITION  OF  THE 
MOLECULE. 

This  reaction  is  to  be  observed  in  the  energetic  reduction 
of  hydrazo  compounds  with  tin  and  hydrochloric  acid  in  a 
sealed  tube.  Hydrazo  derivatives  are  reduced  similarly  when 
they  are  heated : 

/C6H5.NH\     C6H5.N    C6H5.NH2 

2  I       =  11  + 

\C6H5.NH/    C6H5.N    C6H5.NH2. 

Hydrazo-benzene.     Azobenzene.  Aniline. 

The  products  of  the  condensation  of  aldehydes  with  hydra- 
zines  are  decomposed  in  the  same  manner.  Ordinary  aldehyde 
combined  with  phenyl-hydrazine  gives  a  compound  which,  with 
sodium  amalgam,  is  decomposed  into  aniline  and  ethylamine: 

CH3.CH :  N.NH.C6H5 + 2H2  =  C6H5.NH2  +  CH3.CH2.NH2. 

Hydrazines  alone  are  decomposed  in  a  similar  manner.  By 
prolonged  boiling  on  a  water  bath  with  zinc  dust  and  hydro- 
chloric acid,  phenyl-hydrazine  is  decomposed  into  ammonia  and 
aniline : 

C6H5.HN  -  NH2  +  H2  =  NH3  +  C6H5.NH2. 

Reduction  with  evolution  of  ammonia  also  takes  place 
by  the  action  of  ammonia  on  cyan-phenine, 

(C6H5.CN)  3  +  2H2  =  NH3  +  C6H5.C.NHX 

II         >.C6H5 
C6H5C.N   ' 

Lophine. 

and  by  the  reduction,  with  fixation  of  water  (by  sodium  amal- 
gam), of  the  cinchomeronic  acids  (pyridine  carboxylic  acid): 

C7H504N  +  H20  +  H2  =  C7H605  +  NH3. 


CHAPTER  III. 
SUBSTITUTIONS. 

I.  LAWS  OF  SUBSTITUTIONS. 

BY  the  action  of  chlorine  on  hydrocarbons  of  a  normal 
chain,  there  are  usually  obtained  two  substitution  products: 

R.CH2.CH2.C1   and   R.CH<  pL  ,  while    with    bromine    there 


is   almost   exclusively  obtained  R.CH-r  .    Ethyl  benzene 


behaves  in  the  same  manner  on  chlorination  or  bromination 
in  sunlight;    there  is  formed  exclusively  chlor-ethyl-benzene, 

C1 

P     ,  or  the  corresponding  bromine  derivative. 


Secondary  hydrocarbons  are  substituted  by  chlorine  at 
the  carbon  atom  containing  the  least  number  of  hydrogen 
atoms: 

(CH3)3.CH      gives      (CH3)C.C1. 

Isobutane.  Tertiary  butyl  chloride. 

On  further  action  the  chlorine  attaches  to  the  carbon  atom 
which  adjoins  that  one  already  linked  to  a  halogen.  In 
certain  cases,  however,  this  rule  does  not  hold. 

1st.  With  ethylidene  chloride,  CH3.CH.C12,  besides  tri- 
chlor-e  thane,  CH3.CC13,  there  is  produced  at  the  same  time 
chlor-ethylene  chloride,  CH2C1.CHC12. 

2d.  During  the  chlorination  in  sunlight  of  iso-propyl 
chloride,  CH3.CHC1.CH3,  there  is  formed,  simultaneously  with 
iso-propylidene  chloride,  CH3.CC12.CH3,  a  certain  quantity  of 
propylene  chloride,  CH3.CHC1.CH2.C1.  The  latter  is  formed 
exclusively  with  iodine  chloride,  IC1  (at  100°  C.)  ;  by  the 
•continued  action  of  iodine  chloride,  this  is  finally  converted 

67 


68  ORGANIC  SYNTHESES. 

into  trichlorhydrin  of  glycerol,  CH2C1.CHC1.CH2.C1.  This  re- 
action  is  interesting,  as  it  allows  of  the  synthesis  of  glycerol. 

3d.  Ethyl  bromide,  C2H5.Br,  at  200°  C.,  with  bromine 
gives  ethylidine  bromide,  CH3.CHBr2;  but  in  the  presence 
of  aluminium  bromide,  Al2Br6,  there  is  formed  only  the  bromide 
of  ethylene,  CH2Br.CH2Br.  Propyl  and  iso-propyl  bromides. 
CH3.CH2.CH2Br,  and  CH3.CHBr.CH3,  on  bromination,  both. 
yield  the  same  propylene  bromide,  CH3.CHBr.CH2Br. 

Fatty  acids  with  halogens  yield  principally  the  a-deriva~ 
tives.  Propionic  acid  with  bromine  gives  the  a-brom  and  a-di- 
brom-propionic  acids: 

CH3.CHBr.COOH    and    CH3.CBr2.COOH. 

The  aromatic  series  affords  the  most  general  laws.1  It 
may  be  said  that  usually  the  introduction  into  a  compound  of 
substituents  of  the  first  group, 

Cl,  Br,  I,  OH,  NH2,  CnH2n+1,  OR,  NHR,  NH-COR, 

will  usually  cause  the  second  substituting  group  to  go  to  the 
ortho  and  para  positions,  while  substituents  of  the  second 
group, 

N02,  S03H,  COOH,  CHO,  CO,  CN,  CH3.CO,  etc., 

will  usually  form  meta  compounds  with  the  second  radical. 
Thus,  chlor-benzene,  C6H5C1,  with  nitric  acid,  gives  a  mixture 
of  ortho-  and  para-chlor-nitrobenzenes  : 

rH/(D  Cl  ,    rH/(D  Cl 

CeH4\(2)  N02    and    CeH4\(4) 


With  sulphuric  acid,  it  gives  para-chlor-benzene  sulphonic  acidr 
<^  \.l  ~~  ^yry.    Phenol  with  nitric  acid  gives  ortho-nitro- 

((^ 
Nitro-benzene  with  nitric  acid  yields  principally  meta-dinitro- 

1  See  Armstrong,  Jour.  Chem.  Soc.,  1887. 


phenol,  C6H4<  >  and  Para-nitro-phenol,  C6EL 


SUBSTITUTIONS.  69 

benzene,  CeH^/J  NQ2,  with   but   a  small   amount  of   the 

ortho  and  para  isomers.     Occasionally    two    different    groups- 
have  the  same  action  on  the    substituant.    Thus,  para-nitro- 


/(\\ 


toluene,  C6H4<    )7\  nn>  on  chlorination  gives  C6H3-(2)  Cl 


4        \ 


4)  N02 


</-| 
(3)  NO      '    on 
/(I)  C02OH 
yields  C6H3^-(3)  N02      .    Sometimes,  however,  the  action  is- 

\5)  N02 
different,  and  then  isomers  are  formed.    Thus,  if  brom-nitro- 

//1\   /~^TT 

toluene,  CeHty  ),<  -g   3,  is   treated  with   sulphuric   acid,  the 

CH3  group  has  the  tendency  to  make  the  sulphonic  acid  group 
take  the  positions  2  or  6,  while  that  of  the  bromine  would 
make  it  take  positions  3  or  5,  and,  as  a  result,  two  isomers  are 
formed.  It  may  happen  that  the  influence  of  one  group  is 
stronger  than  that  of  another,  as  in  the  case  of  para-brom- 
aniline,  where  NH2  has  more  influence  than  Br,  and  hence 

/(I)  NH2 
on  nitration  there  is  formed  CeH3^-(2)  N02.     In  the  same 

\(4)  Br 
way  OH  and  NH.CO.CH3  have  more  influence  than  CH3. 

External   conditions   also   have   an  influence   on   the  for- 
mation of  isomers.    Thus,  phenol  in  the  cold,  with  sulphuric 

acid,  gives  principally  aseptol,  C6H4<^Lx  gQ  QJJ,  and  with  ni- 
tric acid  it  gives  C6H4<^  )  .(  -J^Q  ;  if  heat  is  employed,  howeverr 


in  the  first  case,  para-phenol-sulphonic  acid,  C6H4<('  \X  ^ 

will  be  formed,  and,  in  the  second  case,  ortho-nitro-phenolr 

r  TT  /(I)  OH 
CeH4\(2)  N02' 

The    action    of   halogens    on    the    aromatic    hydrocarbons 
will  differ  according  to  the  temperature  and  the  conditions 


70  ORGANIC  SYNTHESES. 

of  light,  and  there  will  correspondingly  be  produced  substitu- 
tions in  the  nucleus  or  in  the  side-chains.  If  chlorine  is  allowed 
to  act  on  boiling  toluene,  or  on  its  vapors,  or  even  when  cooled 
to  zero  but  in  direct  sunlight,  the  side-chain  will  suffer  substi- 
tution; the  principal  product,  for  example,  being  benzyl 
chloride,  C6H5.CH2.C1.  At  the  ordinary  temperature,  or 
•even  with  heat,  but  in  the  presence  of  a  chlorine  carrier,  the 
substitution  takes  place  in  the  nucleus,  and  chlor-toluene, 

/PH 
C6H4<^Qi  3,  is  formed.     Bromine  acts  in  the  same  manner. 

In  certain  cases,  external  conditions  only  influence  the 
rapidity  of  the  reaction,  but  not  its  direction.  Thus,  dry 
chlorine  on  acetophenone,  C6H5.CO.CH3,  whether  cold  or  hot, 
in  sunlight  or  in  the  dark,  gives  principally  the  "compound 
C6H5.CO.CH.C12. 

II.  SUBSTITUTION  OF  CERTAIN  ELEMENTS  OR  GROUPS 
BY  OTHERS. 

A.  Preparation  of  Halogen  Compounds. 

The  exchange  of  hydrogen  for  a  halogen  frequently  takes 
place  by  direct  action  at  15°  C.,  or  by  heating  (as  when  the 
vapors  of  a  body,  mixed  with  chlorine  or  bromine,  are  allowed 
to  pass  through  animal  charcoal  heated  to  250-400°  C.).  The 
presence  of  certain  bodies  greatly  facilitates  the  formation  of 
substituted  halogen  compounds.  Iodine,  or  the  chlorine  and 
bromine  compounds  of  molybdenum,  iron,  aluminium,  and 
.antimony,  aid  considerably  in  bromination  or  chlorination. 
Ferric  chloride  is  also  an  agent  for  bromination  or  iodination, 
but  it  does  not  remain  unaltered  as  in  chlorination,  or  as  is 
the  case  with  most  agents  serving  as  halogen-carriers.  Sul- 
phuric acid  also  acts  as  a  carrier  of  iodine.  The  bromination 
of  nitro-benzene  in  the  presence  of  ferric  chloride  may  be 
expressed  by  the  equation: 

6C6H5N02 + 6Br2  +  Fe2Cl6  =  GC^/^32 + Fe2Br6  +  6HC1. 
An  analogous  reaction  occurs  in  that  of  iodine   on   benzene 


SUBSTITUTIONS.  71 

In  the  presence  of  ferric  chloride,  but  the  quantity  of  iodo- 
benzene  produced  is  very  small.  The  ferric  chloride  should 
be  absolutely  dry,  else  the  reaction  will  take  place  in  another 


</-i  \ 
(A\ 
(4;  2 


heated  with  bromine  and  moist  ferric  chloride,  it  is  converted 

/  (\\  CTT  PI 
into  para-nitro-benzyl-chloride,  C6H4<    )  ,(  -2    . 


, 

In  certain  cases,  to  chlorinate  a  body  it  is  heated  in  a  sealed 
tube  with  iodine  trichloride,  antimony  pentachloricle,  phos- 
phorus pentachloride,  or  calcium  hypochlorite.  There  may  also 
be  employed,  as  a  source  of  chlorine,  a  mixture  of  hydrochloric 
-acid  and  manganese  dioxide,  or  potassium  bichromate  with 
potassium  chlorate. 

//-i\    PTT 

On  heating  xylene,  CeH^  \1  CH3,  with  phosphorus  penta- 

chloride at  190-195°  C.,  according  to  the  quantity  chlorinated, 

•   t        j  n  XT  /(I)  CHo-Cl  n  TT  /(I)  CHC12 

there  is  formed  CeHX  J^c  ^    Q  or  even  C6H4<T  }/  CHCl 

Iodine  trichloride  though  acting  as  a  chlorine  carrier,  in 
certain  cases  also  gives  iodine  substitution  products.  For 

example,  CO/£^  with  IC13  gives 

The  addition  of  water  favors  bromination.  The  presence  of 
red  phosphorus  allows  of  the  preparation  of  bromine  com- 
pounds without  heating  in  a  sealed  tube.  The  hydrobromic 
acid  which  is  liberated  during  bromination  may  cause  secondary 
reactions,  —  for  example,  reduction  of  the  N02  group.  Thus,  by 
the  action  of  bromine  on  nitro-benzene  in  the  presence  of  bro- 

mine carriers,  there  is  formed  brom-nitro-benzene,  C6H4< 
and    simultaneously    there    is    also    formed    tribrom-aniline, 
tetrabrom-aniline, 

.2 

Nitro  compounds,  when  brominated  or  chlorinated,  often 
exchange  their  N02  group  for  a  Br  or  Cl.  Thus,  with  the 
nitro-benzoic  acids,  there  is  formed  brom-benzoic  acid  and 


72  ORGANIC  SYNTHESES. 

brom-benzene  (resulting  from  the  elimination  of  €62).  The 

sulphonic  acids  behave  somewhat  in  the  same  manner;  with 

bromine  they  give  brominated  compounds  and    at  the  same 
time  exchange  S02.OH  for  Br: 

R.S02OH  +  Br2  +  H20  =  R.Br  +  H2S04  +  HBr. 

The  formation  of  halogen  acids,  during  the  action  of  halo- 
gens, has  a  bad  influence  on  the  reaction,  especially  when 
under  the  influence  of  iodine.  It  is  necessary  in  this  case  to= 
eliminate  the  hydriodic  acid  which  is  formed;  this  may  be 
done  by  adding  with  the  iodine  some  mercury  oxide,  HgO, 
or  iodic  acid,  HIOs.  The  reaction  may  then  be  expressed  as 
follows  : 


2C6H5.OH  +  2I2  +  HgO  =  2C6H4QH  +  HgI2  +  H20. 

5CH3.CHO  +  2I2  +  HI03  =  5CH2/*  HQ  +  3H20. 

Phenols  and  the  aromatic  oxy-acids  react  readily  with  iodine 
and  iodic  acid.  With  hydrocarbons  and  carboxylic  acids, 
it  is  necessary  to  heat  them  with  the  same  reagents  in  sealed 
tubes  to  200-240°  C.  Iodine  and  mercuric  oxide  may  also 
be  made  to  react  in  alcoholic  solution  or  in  glacial  acetic  acid. 
Solvents  serving  for  chlorination  are  chloroform  and  carbon 
disulphide,  never  alcohol  or  ether;  for  bromination,  besides- 
the  preceding,  there  may  also  be  used  glacial  acetic  acid  or 
petroleum  ether.  Salicylic  acid  is  converted  into  iodo-salicylic 
acid  when  heated  with  an  alcoholic  solution  of  iodine.  It 
is  probable  that  the  hydriodic  acid  formed  is  decomposed  by 
the  alcohol;  for  otherwise  it  would  reduce,  even  below  100°  C., 
the  iodo-salicylic  acid  to  salicylic  acid  again. 

lodination  is  readily  performed  by  means  of  iodine  chloride,. 

Id.     Thus,    C6H5.CH3+ICl  =  HCl+C6H4<^jH3.     Some   acids 
may  be  brominated  or  iodinated  by  the  action  of  bromine  or 


SUBSTITUTIONS.  73 

iodine  on  their  silver  salts: 

f°OH+AgI. 

Certain  acids,  however,  behave  differently.    The  salt  of  phthalic 
acid  is  decomposed  with  the  formation  of  the  anhydride  : 


The  halogen  sometimes  reacts  so  energetically  that  it  is 
difficult  to  obtain  monohalogen  substituted  products,  —  for 
example,  the  chlorination  of  aromatic  amines  (see  page  74 
for  the  aliphatic  amines).  Aniline,  C6H5.NH2,  with  chlorine, 

<C1 
-jyrTT  .    To   prepare 

/Cl 
chlor-aniline,  CeH^  MTT  ,  it  is  necessary  to  first  transform  the 

\1M±12 

aniline  into  an  anilide,  then  chlorinate,  and  finally  saponify. 
The  alcohols  of  the  paraffin  series,  by  reason  of  the  oxi- 
dation which  accompanies  chlorination,  give  chlor-aldehydes. 
By  the  action  of  chlorine  on  ethyl  alcohol,  it  may  be  supposed 
that  there  is  formed  a  chlor-ethyl  alcohol,  which  is  decom- 
posed into  aldehyde  and  hydrochloric  acid: 


CH3.CH2.OH          -»   CH3.CH  --»  CH3.CHO. 


The  chlorine  substitution  products  of  the  alcohols  are  only 
formed  from  polyatomic  alcohols  or  chlor-aldehydes. 

In  certain  rare  cases,  the  hydrogen  not  linked  to  carbon 
may  be  replaced  by  a  halogen.  Phenol,  or  its  tribrom-  or 
trichlor-derivatives,  with  an  excess  of  bromine  water,  has  its 
phenolic  hydrogen  replaced  by  bromine  :  1 

1  This  characteristic  reaction  of  the  phenol  is  based  on  the  formation  of  the 
tribrom-phenol  bromide,  and  not  on  the  formation  of  tribrom-phenol.  The  tri- 
brom-phenol  bromide,  C6H2Br3.OBr,  is  not  attacked  by  boiling  alkalies;  its  solu- 


74  ORGANIC  SYNTHESES. 

OH  +  Br2  "  C6H2\OBr  +  HBr' 

The  aromatic  sulphonic  acids,  with  bromine,  yield  compounds 
in  which  the  acid  hydrogen  is  replaced  by  bromine  : 

C6H5.S02OH    -5^->    C6H5.S02.OBr  +  HBr. 

In  acid  amides,  the  halogen  replaces  the  hydrogen,  attached 
to  the  nitrogen,  by  action  in  alkaline  solution.  Thus,  with 
acetamide,  CH3.CO.NH2,  there  is  formed  acetbromamide, 
CH3.CO.NHBr;  these  compounds  are  difficult  to  isolate  on 
account  of  their  ready  decomposition.  The  paraffin  amines, 
with  halogens,  exchange  a  hydrogen  in  the  NH2  group.  Thus, 
by  passing  chlorine  into  an  aqueous  or  alkaline  solution  of 
ethylamine  here  is  formed  ethylamine  dichloride,  C2H5.NC12. 


B.  Exchange  of  Halogens  for  One  Another. 

The  action  of  chlorine  on  brom-  and  iodo-compounds  does 
not  cause  a  displacement  of  hydrogen,  but  an  exchange  of  bro- 
mine or  iodine  for  chlorine;  so,  in  order  to  have  chlor-brom-  or 
chlor-iodo-compounds,  it  is  necessary  to  first  introduce  chlorine.1 

The  substitution  of  bromine  by  chlorine  is  effected  by 
the  aid  of  the  pentachlorides  of  antimony  and  phosphorus. 
Thus: 

2C2H5Br  +  SbCl5  -  2C2H5C1  +  Br2  +  SbCl3  . 

Ethylene  bromide,  according  to  the  quantity  of  pentachloride 

tion  in  benzene  is  decomposed  by  caustic  potash,  giving  C0H2Br3.OH.      With 
potassium  iodide  it  reacts  according  to  the  following  equation: 

C6H2Br3.OBr+  2KI=  C6H2Br3.OK+  12. 

1  This  reaction,  however,  may  be  used  for  obtaining  chlorine  substitution 
products:  instead  of  allowing  chlorine  to  act  "directly  on  the  body,  the  liquid 
iodine  derivatives  are  used,  kept  under  water,  and  heated  with  chlorine  water 
until  liberation  of  iodine  has  ceased.  In  the  aromatic  series,  only  iodo- 

aniline,  CaH4!         2  undergoes  this  reaction. 


SUBSTITUTIONS.  75 

of  antimony  used,  is  converted  into  ethylene  chlor-bromide, 
CH2.C1  CH2.C1 

I  or  ethylene  chloride,  |  ;  while  with  methyl  or  ethyl- 

CH2Br  CH2.C1 

dibromides,  CH2Br2  and  CH3.CH.Br2,  the  two  bromine  atoms 
are  replaced  at  once.  Bromine  can  also  be  replaced  by  heat- 
ing the  compound  gently  with  mercuric  chloride,  HgCl2 : 

2CH3.CHBr  .CH2Br  +  HgCl2  -  2CH3  .CHCl.CH2Br  +  HgBr2. 

Iodine  is  still  more  readily  replaced  by  chlorine,  not  only 
by  the  direct  action  of  the  latter,  but  also  by  the  double  decom- 
position of  an  iodine  compound  with  certain  metallic  chlorides, 
like  mercuric  chloride,  HgCl2,  the  mixture  being  heated  in 
the  presence  of  water  or  ether.  lodoform,  under  these  con- 
ditions, only  has  two  iodine  atoms  replaced,  giving  CHIC12. 

The  substitution  of  chlorine  by  bromine  takes  place  by 
the  direct  action  of  bromine  only  in  the  case  of  acid  chlorides 
(which  then  behave  like  chloric  acid,  in  which  the  chlorine  is 
replaced  by  bromine),  and  in  some  other  cases  by  double 
decomposition.  Thus,  chlor-acetic  acid,  CH2C1.COOH,  heated 
to  150°  C.  in  a  sealed  tube  with  hydrobromic  acid  or  potassium 
bromide,  is  converted  into  brom-acetic  acid,  CH2.Br.COOJL 
The  acid  chlorides,  on  the  contrary,  under  these  conditions 
do  not  react:  for  instance,  acetyl  chloride,  CH3.CO.C1,  heated 
for  several  hours  at  100°  C.  with  potassium  bromide,  is  not 
changed.  Aluminium  bromide  readily  attacks  alkyl  chlorides; 
by  its  action,  carbon  tetrachloride,  CCL*,  is  converted  into  the 
tetrabromide,  CBr4.1 

Iodine  replaces  chlorine  when  compounds  of  the  latter 
(except  in  the  aromatic  series)  are  treated  with  hydriodic  acid 
or  metallic  iodides  CeHs.Cl  when  heated  with  H  for  fifteen 
hours  at  235°  C.,  gives  C6H6  +  HC1  +  I.)  The  reaction  takes 
place  in  the  cold  without  an  excess  of  acid.  For  unsaturated 

1  For  the  preparation  of  the  halides  of  aluminium  and  their  application  to 
halogen  substitution  products,  see  Gustavsonn,  Action  of  the  Halogen  Salts  of 
Aluminium  on  Organic  Compounds,  Moscow,  1883  (in  Russian). 


76  ORGANIC  SYNTHESES. 

compounds,  or  those  containing  OH  (which  can  fix  HI  or 
exchange  OH),  potassium  iodide  may  be  used,  under  100°  C. 
in  alcoholic  solution.  Calcium  iodide,  Cal2,  may  also  be  used 
(see  replacement  of  bromine  by  iodine). 

The  best  method  of  converting  the  higher  chlorine  deriva- 
tives into  iodine  compounds  is  to  use  aluminium  iodide  dis- 
solved in  carbon  disulphide.  Ethylidine  chloride,  CH3.CHCl2, 
becomes  ethylidine  iodide,  CH3.CHI2.  The  trichlorhydrin  of 
glycerol  with  aluminium  iodide  gives  allyl  iodide, 
CH2  =  CH.CH2I,  together  with  aluminium  chloride  and  iodine. 

Iodine  is  replaced  by  bromine  by  the  direct  action  of  the 
latter,  or  by  boiling  with  bromine  water,  or  by  double  decom- 
position in  a  sealed  tube  with  metallic  bromides,  such  as  those 
of  mercury,  copper,  or  silver.  For  example: 

2CH3.CHLCH3  +  HgBr2 = 2CH3.CHBr.CH3  +  HgI2. 

In  the  higher  substitution  products,  iodine  may  be  replaced 
in  part  or  completely.  Thus: 

2CHI3  +  Br2 = 2CHI2Br + 12. 

Sometimes,  by  the  action  of  the  hydriodic  acid,  there  is 
formed  an  unsaturated  compound  which  combines  with  the 
bromine.  For  this  reason,  by  the  action  of  bromine  on  sec- 
ondary butyl  iodide,  CH3.CH2.CHI.CH3,  there  is  formed 
CH3.CHBr.CHBr.CH3.  Iodine  occurring  in  the  aromatic 
nucleus,  in  general,  is  not  replaceable  by  bromine;  but  the 
latter  acting  on  iodo-aniline  gives  tribrom-aniline : 


NH 


n  TT  /  Br3 
>  ^6ki.2< 


Bromine  and  chlorine  are  replaced  by  iodine  by  double 
decomposition  with  the  iodides  of  potassium  or  calcium.  The 
bromine  compounds  are  heated  with  calcium  iodide  (dried 
with  exclusion  of  air)  in  sealed  tubes,  generally  below  100°  C. 


SUBSTITUTIONS.  77 

In  this  manner,  propyl  bromide,  CHa.CHBr.CHs,  is  converted 
into  the  iodide,  CH3.CHI.CH3.  On  account  of  the  insta- 
bility of  di-iodo  compounds  in  which  the  iodine  occurs  attached 
to  adjoining  carbon  atoms,  these  bodies,  at  the  moment  of 
their  formation,  are  decomposed  into  unsaturated  derivatives 
and  iodine  is  set  free. 

The  substitution  of  chlorine  and  iodine  by  fluorine  takes 
place  by  double  decomposition  of  chlorine  compounds  with 
arsenic  fluoride,  or,  in  the  case  of  iodine  compounds,  with  silver 
fluoride, 

C2H5I+AgF  =  C2H5F+AgI. 

C.  The  Substitution  of  Other  Groups  by  Halogens. 

The  replacement  of  NH2  by  a  halogen  is  accomplished  through 
the  diazo  compounds  by  the  conversion  of  the  NH2  into  N  :N.R, 
and  subsequently  replacing  this  group  with  a  halogen.1  The 
halogen  derivatives  of  the  diazo  bodies,  such  as  diazo-benzene 
chloride,  C6H5.N:N.C1,  are  directly  decomposed  on  heating, 
giving,  in  the  case  quoted,  chlor-benzene,  C6H5C1  and  N2. 
The  halogen  substitution  products  of  benzene  and  its  deriva- 
tives are  also  obtained  by  heating  a  diazo  salt  (sulphate  or 
nitrate)  with  concentrated  halogen  acids  (instead  of  the  aqueous 
solution  of  hydrochloric  acid,  its  acetic  acid  solution  may  be 
used)  : 


The  best  means  of  preparing  the  chlorine  substitution  deriv- 
atives is  to  prepare  the  chlor-platinate  of  the  diazo  body; 
the  precipitate  is  difficultly  soluble  in  alcohol,  and  is  collected, 
dried,  and  heated  with  ten  times  its  weight  of  a  mixture  of 
dry  soda  and  ground  glass: 


1  The  diazo  derivatives  of  the  aliphatic  series,  treated  with  halogens  or  halogen 
acids,  have  the  N=N  group  directly  replaced  by  a  molecule  of  halogen  or  halogen 
acid. 


7$  ORGANIC  SYNTHESES. 

The  chlor-platinates  may  be  replaced  by  the  double  salts 
of  the  diazo-chlorides  with  the  cuprous  salts  of  chlorine  or 
bromine,  Cu2Cl2  and  Cu2Br2. 

To  the  cold  solution  of  the  amine  in  dilute  hydrochloric 
acid,  there  is  added,  little  by  little,  the  theoretical  quantity 
of  sodium  nitrite,  and  then  a  solution  of  hydrochloric  acid 
heated  with  cuprous  chloride  is  gradually  added.  The  double 
compound  which  is  formed  is  generally  decomposed  with  dis- 
engagement of  nitrogen,  producing  the  chloride  and  cuprous 
chloride,  which  readily  separates  out,  owing  to  its  insolubility. 

Halogen  substitution  products  can  also  be  obtained  by 
the  action  of  halogen  acids  on  diazo-amido  compounds.  This 
is  the  best  means  of  preparing  iodine  and  fluorine  compounds. 
Thus,  benzene  fluoride,  C6H5F,  is  prepared  by  the  action  of 
hydrofluoric  acid  on  C6H5N:N.NC5Hio.  The  latter  body 
is  produced  by  the  action  of  diazobenzene  chloride  on  piperi- 
dine.  For  preparing  bromine  compounds  there  may  be  utilized 
the  decomposition  of  the  perbromides,  which  are  formed  by  the 
action  of  bromine  in  hydrobromic  acid  solution  on  an  aqueous 
solution  of  the  diazo  sulphate.  The  compound  is  washed 
with  alcohol  and  dried.  On  heating,  alone  or  with  glacial  acetic 
acid,  it  is  decomposed  according  to  the  equation: 

C6H5N :  N.Br  .Br2 = C6H5Br + N2 + Br2. 

The  substitution  of  the  -N  =  N-  group  by  halogens  or 
halogen  acids  takes  place  by  the  action  of  these  on  the  diazo 
compounds  of  the  aliphatic  series.  Thus,  diazo-acetic-ester 
gives  di-iodo-acetic-ester  with  iodine  in  alcoholic  solution  and 
at  the  ordinary  temperature;1  by  the  action  of  hydrochloric 
acid  it  gives  chlor-acetic  ester. 

CHN2.CO.OR+I2=CHI2.CO.OR+N2, 
CHN2.CO.OR  +  HC1  =  CHaCl.CO.OR  +  N2. 

1  Titration  with  iodine  is  used  in  the  quantitative  determination  of  the  diazo 
compounds  of  the  aliphatic  series. 


SUBSTITUTIONS.  79 

Substitution  of  OH  by  a  halogen.  —  The  alcoholic  OH 
group  is  replaced  by  halogens  on  treatment  with  a  concen- 
trated halogen  acid,  or  with  a  mixture  which  liberates  such 
acids  (NaCl  and  H2S04;  KBr  and  H2S04). 

With  hydrochloric  acid  the  action  is  quite  slow,  arid  heat 
is  generally  required  to  bring  about  the  reaction,  either  in  a 
sealed  tube  or  in  the  presence  of  dehydrating  agents.  Hydro- 
bromic  acid  reacts  more  easily,  and  hydriodic  acid  still  more 
so,  and  in  the  latter  case  it  is  not  always  necessary  to  use  heat, 
Instead  of  acids,  bromine  or  iodine  may  also  be  allowed  to  act 
on  the  alcohols  in  the  presence  of  phosphorus. 

It  must  not  be  forgotten  that  an  excess  of  acid  may  act 
as  a  reducing  agent.1  In  certain  cases  this  reaction  takes 
place  more  easily  than  that  of  replacing  OH  by  I.  Thus, 
iod-acetic  acid,  CH2I.CO.OH,  reacts  in  the  cold,  even  with 
sufficiently  diluted  hydriodic  acid;  while  glycollic  acid, 
CH2(OH).CO.OH,  only  reacts  when  heated  with  concen- 
trated acid.  This  is  why  iod-acetic  acid  is  not  formed  by  the 
action  of  hydriodic  acid  on  glycollic  acid.  Lactic  acid  behaves 

in  the  same  manner,  which  distinguishes  it  from  the  iosmeric 

/pTT  r\Ti 
hydracrylic  acid,  CH2\2       ,  which  readily  forms  an  iodide, 


Compounds  rich  in  hydroxyl,  with  hydriodic  acid,  readily 
exchange  one  or  more  of  their  OH  groups  for  H,  by  reason 
of  the  reaction  of  the  acid  with  the  iodo  product:  thus,  with 
glyceric  acid  is  obtained  /9-iodo-propionic  acid,  CH2LCH2.CO.OH; 
the  iodine  which  occurs  in  the  primary  group  is  always  the 
more  stable.  In  polyatomic  alcohols,  on  the  contrary,  the 
iodine  which  is  found  in  the  secondary  group  (called  beta) 
shows  the  greater  stability.  If  in  the  compound  there  are 
several  hydroxyl  groups,  according  to  the  conditions  of  the 
experiment,  it  is  possible  to  replace  all  or  some  of  them  with 
chlorine.  For  an  incomplete  exchange,  there  may  be  used, 
among  others,  sulphur  chloride,  S2C12,  which  reacts,2  for  exam- 

1  See  substitution  of  iodine  by  hydrogen. 

2  The  product  obtained  always  contains  sulphur. 


•So  ORGANIC  SYNTHESES. 

pie,  with  glycol,  according  to  the  equation: 

CH2.OH  CH2C1 

2  1  +232C12  =  2|  +  HC1+S02 

CH2.OH  CH2.OH 

Instead  of  using  the  halogen  acids,  the  different  halogen 
compounds  of  phosphorus  may  be  used,  which  react  with  great 
energy.  In  certain  bodies,  as,  for  example,  phenols,  carboxylic, 
and  sulphonic  acids,  it  is  only  by  this  means  that  OH  may 
be  exchanged  for  a  halogen.1  The  trichloride  of  phosphorus 
is  used  in  cases  where  other  reactions  than  the  exchange  of 
OH  may  take  place,  such  as  the  fixation  of  hydrochloric  acid. 
Propargyl  alcohol  reacts  according  to  the  following  equation: 


Sometimes  the  action  of  the  trichloride  leads  to  the  for- 
mation of  anhydrides,  as  with  benzhydrol  : 

(C6H5)2CH.OH,    gives  [(C6H5)2CH]20. 

The  pentachloride  is  usually  applied  in  cases  where  the 
body  contains  several  hydroxyl  groups  and  it  is  necessary  to 
replace  them  all;  erythrite,  for  example,  gives  erythrene  tetra- 
chloride,  C^eOU.  The  pentachloride  and  pentabromide  of 
phosphorus  are  used  for  the  replacing  of  OH  by  Cl  and  Br 
in  phenols  and  in  carboxylic  and  sulphonic  acids.  In  aliphatic 
acids,  the  same  result  is  gained  by  the  action  of  PClsor  POCls.2 

1  The  OH  of  carboxylic  acids  may  be  replaced  by  chlorine  with  hydrochloric 
acid  only  in  the  presence  of  phosphoric  anhydride.     Thus,  by  passing  a  current 
of  the  gas  into  glacial  acetic  acid  mixed  with  P2O5,  acetyl  chloride  is  formed 

.even  at  0°  C.     But  benzoyl  cloride  can  only  be  obtained  by  passing  hydrochloric 
acid  gas  into  a  mixture  of  benzoic  acid  and  P2O5  heated  to  200°  C. 

2  For  the  preparation  of  the  acid  bromides,  in  place  of  PBr3,  it  is  more  con- 
venient to  use  a  mixture  of  the  acid  with  phosphorus,  while  bromine  is  added 
from  time  to  time  in  quantity  corresponding  to  the  equation: 

3RCO.OH+2PBr3=3R.COBr+3HBr+P2O3. 


SUBSTITUTIONS.  81 

By  the  action  of  PC15  on  the  oxy-acids,  the  hydroxyl  groups 
are  replaced  by  Cl.  The  aromatic  oxy-acids  at  first  give  com- 
binations which  contain  phosphorus  and  chlorine  like 


PC\s,  which  finally  become,  by  the  action  of  the 
0 
pentachloride  or  simply  by  the  action  of  heat,   chlorinated 

/COC1 
acid  chlorides,  CeH^  ™          Glycollic  acid  gives  chlor-acetyl- 

chloride,  according  to  the  following  equation: 

CH.OH  CH2.C1 

|  +2PC15  =  |  +2POC13  +  2HC1. 

CO.OH  CO.C1 

The  same  reaction  takes  place  with  the  perbromide. 

In  order  to  obtain  a  brom  derivative  of  an  oxy-acid,  it  is 
necessary  to  heat  the  latter  with  hydrobromic  acid,  or  to  use 
the  perbromide  with  the  ether  of  the  oxy-acid.  Thus: 

CH2.OH  CH2.Br 

H-PBrsH  +POBr3  +  HBr. 

CO.OC2H5  CO.OC2H5 

With  certain  polybasic  oxy-acids  there  are  formed  unsatu- 
rated  derivatives  of  the  acids:  thus,  malic  acid  gives  fumaryl 
chloride*  tartaric  acid  is  converted  into  chlor-malyl  chloride; 

CO.OH  CO.C1 

CH.OH  CH 

|  +3PC15  =  ||         +3POC13+4HC1. 

CH2  CH 

I  I 

CO.OH  CO.C1 

Replacing  a  halogen  by  OH.     (See  Chapter  on  Oxidation.) 

The  replacing  of  0  in  the  CO  group  of  aldehydes,  ketones, 
ketonic  acids,  and  other  compounds  by  Cl  or  Br  is  done  by 


82  ORGANIC  SYNTHESES. 

using  the  perchloride  or  perbromide  (it  is  better  to  take  the 
chlor-bromide,  because  it  is  easier  to  separate  the  oxychloride 
by  oxidation).  The  reaction  takes  place  in  the  cold;  often 
it  is  necessary  to  moderate  the  temperature  by  cooling,  or  by 
addition  of  oxychloride;  in  certain  cases  it  is  necessary  to 
heat  either  under  ordinary  pressure  or  in  sealed  tubes.  During 
this  reaction  the  halogen  acid  is  some  tunes  disengaged. 

The  replacing  of  0  by  I2  cannot  be  done  directly.  It 
is  necessary  to  operate  indirectly  by  first  splitting  off  water, 
then  treating  with  hydriodic  acid,  which  is  then  fixed  by  the 
unsaturated  body  : 

CH3.CO.CH3  -  H20  =  CH3  .C  =  CH, 


D.  Preparation  of  the  Derivatives  of  Nitrous  and  Nitric  Acid? 
and  of  Hydroxylamine. 

Replacing  H  by  NO.  —  The  introduction  of  the  NO  group 
by  the  substitution  of  hydrogen  linked  to  a  carbon  atom  only 
takes  place  in  a  few  cases.  It  is  believed  that  this  reaction 
occurs  when  mixture  of  potassium  nitrite  and  sulphuric  acid 
is  allowed  to  act  on  an  alkaline  solution  of  secondary  nitro 
compounds,  such  as  nitro-isopropane,  (CH3)2CH.N02,  which 
is  converted  into  isopropyl-pseudonitrol,  (CH3)2C(NO)N02.1 

1  Nitro  compounds  are  differently  affected  by  nitrous  acid,  according  to- 
whether  they  are  primary,  R.CH2.NO2,  secondary,  K2:CH.NO2,  or  tertiary, 
R3  j  C.NO2.  Primary  nitro  compounds  are  converted  into  nitrolic  acids  (oximid- 
compounds)  which  dissolve  in  alkalies  with  an  intense  red  color: 


CH3.C;H2j.N02+|OjN.OH  =  C 

Secondary  nitro  compounds  give  pseudo-nitrols,  which  are  soluble  in  alkalies, 
giving  a  deep  blue  color: 


Tertiary  nitro  compounds  do  not  react  with  nitrous  acid.  These  reactions 
afford  a  delicate  method  .of  detecting  primary,  secondary,  and  tertiary  alcohols; 
the  alcohols  are  first  converted  into  iodides  (with  PI3),  and  then  treated  with 


SUBSTITUTIONS.  83 

Certain  aromatic  tertiary  bases,  such  as  dimethyl-aniline, 
€6H5N(CH3)2,  are  changed  into  nitroso  derivatives  by  the 
theoretical  amount  of  potassium  nitrite  or  amyl  nitrite  added 
to  their  hydrochloric  acid  solutions,  well  cooled.  This  reac- 
tion does  not  appear  to  be  general;  for  the  ortho-  and  para- 
dimethyl-toluidines  do  not  form  nitroso  derivatives,  while 
the  meta-body  furnishes  C6H3(NO)(CH3)N(CH3)2.  It  is  pos- 
sible that  this  may  not  be  a  nitroso  compound,  but  an  iso- 
nitroso  compound. 

The  nitroso-amines  of  the  aromatic  bases  are  converted  into 
para-nitroso  derivatives,  similar  to  para-nitroso-dimethyl-anil- 
Ine,  by  an  alcoholic  solution  of  hydrochloric  acid.  It  is  thought 
by  some  that  nitroso-dimethyl-aniline  may  be  an  azoxy  deriva- 
tive and  may  have  the  quinonoid  formula 

N=/    N  =  N(CH3)2,  HO.N-/    N)>= 

I      \ — /       I  \ — / 


•which  would  explain  the  formation  of  the  sodium  salt  of  para 
nitroso-monomethyl-aniline  : 


NaO.N=/    N>=N  . 

\OH 


The  other  aromatic  derivatives  either  do  not  react  with 
nitrous  acid,  or  behave  in  quite  a  different  manner.  Thus,  with 
phenol,  there  is  formed  a  body  which  for  long  was  considered 
as  nitroso-phenol,  but  which  is  really  a  quinone-oxime.  Per- 
haps it  is  formed  as  an  isomeride  of  the  isonitroso  compound 

silver  nitrite  (AgNO2).  The  nitro  compounds  which  are  thus  formed  are  dis- 
tilled off  and  mixed  with  potassium  nitrite  and  sulphuric  acid;  on  adding  an 
excess  of  potassium  hydrate  the  liquid  becomes  either  red  or  blue,  or  remains 
unchanged,  according  to  whether  the  alcohol  was  primary,  secondary,  or  ter- 
tiary. Only  the  alcohols  of  low  molecular  weight  show  these  color  reactions. 


84  ORGANIC  SYNTHESES. 

which  may  at  first  be  produced: 


--  >  C6H 

N.OH. 

Nitrous  acid  with  alcohols  of  the  aliphatic  series  simply 
replaces  the  hydrogen  of  the  alcoholic  group  to  form  nitrous 
esters.  These  are  easily  obtained  by  saturating  the  alcohol 
with  N203,  and  the  reaction,  if  necessary,  is  completed  by  the 
aid  of  heat;  or,  better,  to  a  mixture  of  the  alcohol  with  sul- 
phuric acid  and  water,  there  is  added  a  solution  of  potassium 
nitrite,  and  the  ester  formed  is  subsequently  isolated.  A  very 
convenient  method  for  preparing  these  esters  is  to  employ 
the  double  decomposition  between  the  alcohols  and  the  nitrous 
ester  of  glycerine.1 

The  hydrogen  united  to  the  nitrogen  of  imido  compounds 
is  easily  replaced  by  NO  by  the  action  of  nitrous  acid;  ia 
this  manner  are  formed  the  nitrosamines  : 


These  nitrosamines  are  prepared  by  passing  N20a  into 
a  solution  of  the  imide  base  (in  alcohol,  ether,  benzene,  acids, 
etc.).  The  body  produced  is  separated  by  evaporating  the 
solution  or  by  diluting  with  water.  There  may  also  be  used 
potassium  nitrite,  which  is  added  in  the  theoretical  quantity  to> 
a  hydrochloric  acid  solution  of  the  base;  or  the  nitrous  esters 
of  ethyl  and  amyl  alcohol  may  be  employed. 

The  anilides  behave  in  the  same  manner,  but  the  nitrosa 
bodies  .formed  are  distinguished  from  the  nitrosamines  by 
their  instability.  Nitroso-anilide,  (C6H5)(CH3.CO)N.NO,  is 
prepared  by  passing  N20s  into  a  solution  of  the  anilide  in 
glacial  acetic  acid.  Piperidine  and  its  derivatives  (for  example, 
conine  or  ct-propyl-piperidine)  and  tetrahydro-quinoline  also 
give  nitroso  compounds. 

1  Gaz.  chim.  ital..  vol.  15,  p.  351. 


SUBSTITUTIONS.  85 

Substitution  of  H  by  N02. — This  substitution  only  takes: 
place  easily  in  the  aromatic  series  by  the  action  of  nitric 
acid.  In  the  aliphatic  series  nitro  compounds  are  rarely  formed. 
Mention,  however,  may  be  made  of  the  formation  of  C(N02)4, 
nitro-isobutylene,  and  nitro-barbituric  acid;  it  may  also  be 
remarked  that  nitro-styrene  probably  has  the  formula 
C6H5.CH  :CH.N02.  Further  mention  will  be  made  of  those 
compounds,  known  as  dinitroso,  obtained  by  the  action  of 
nitric  acid  on  ketones. 

In  the  aromatic  series,  nitration  is  a  very  general  one.  In 
order  to  nitrate  the  aromatic  hydrocarbons,  they  are  added 
little  by  little  to  fuming  nitric  acid,  and  it  is  better  that  the 
latter  does  not  contain  any  nitrogen  oxides;  or  the  acid  may 
be  added  slowly  to  the  hydrocarbon.  A  sufficient  quantity 
of  water  is  added  to  isolate  the  nitro  derivative.  It  is  often 
easier  to  regulate  the  nitration  by  operating  with  a  glacial 
acetic  acid  solution.  The  nitric  acid  employed  in  the  majority 
of  cases  has  a  density  of  1.50  to  1.52.1  In  the  nitration  of 
benzene,  an  excess  of  benzene  diminishes  the  yield  of  nitro- 
benzene, an  excess  of  acid  increases  it. 

Nitration  in  general  does  not  have  to  be  made  at  elevated 
temperatures;  it  is  often  necessary  to  use  refrigeration,  some- 
times to  0°  C.,  for  nitric  acid  also  acts  as  an  oxidizing  agent;, 
and,  if  the  hydrocarbons  have  side-chains,  they  may  be  con- 
verted into  carboxylic  acids  or  ketones.  The  ease  of  nitra- 
tion increases  with  the  number  of  side-chains.  In  order  to 
obtain  higher  nitro  products,  the  reaction  is  carried  out  with 
a  mixture  of  nitric  and  sulphuric  acids,  or  with  the  aid  of  heat, 
if  necessary.  The  sulphonic  acid  compounds,  if  heated  strongly 
during  nitration,  may  have  their  SOsH  group  replaced.  Thus 
mesitylene  sulphonic  acid,  C6H2(CH3)3S03H,  if  it  is  not  cooled,, 
gives  dinitro-mesitylene,  C6H(N02)2(CH3)3. 

The  nitro-sulphonic  acids,  being  soluble  in  water,  cannot 

1  For  the  action  of  nitric  acid  of  different  concentrations  on  the  aromatic- 
hydrocarbons  and  their  derivatives,  see  Annalen,  vol.  224,  p.  283. 


ORGANIC  SYNTHESES 

be  separated  by  addition  of  the  latter;  in  order  to  accomplish 
this,  the  acid  liquor  is  diluted  with  a  little  water  and  the  excess 
of  nitric  acid  is  evaporated  off  on  a  water-bath. 

Phenols  are  nitrated  so  easily  that  it  is  not  necessary  to 
use  fuming  nitric  acid.  Phenolic  ethers  behave  in  the  same 
manner.  The  amido  compounds  l  react  readily  with  nitric 
acid,  and  give  at  once  higher  nitro  products,  or  even  resinous 
matters  ;  also  it  is  only  necessary  to  use  the  theoretical  quantity 
of  acid  or  to  employ  it  dilute.  With  aniline,  for  example, 
the  amine  is  dissolved  in  a  large  quantity  of  cold  sulphuric 
acid,  and  there  is  added,  little  by  little,  a  mixture  of  the  theo- 
retical quantity  of  nitric  acid  with  sulphuric  acid.  When 
the  reaction  is  finished,  the  mass  is  diluted  with  water,  and 
the  excess  of  acid  neutralized  in  order  to  precipitate  the  nitro- 
amido  compound.  In  the  majority  of  cases  the  amido  com- 
pound itself  is  not  nitrated,  but  the  anilide;  the  reaction  pro- 
ceeds nicely,  and,  according  to  the  concentration  of  the  acid, 
either  mono-  or  dinitro  products  can  be  obtained.  The  N02 
group  always  replaces  the  hydrogen  in  the  benzene  nucleus 
of  the  base,  even  in  the  case  where  the  anilide  contains  the 
residue  of  an  aromatic  acid.  The  anilides  of  the  oxy-benzoic 
acids  offer  an  exception;  in  the  nitration  of  salicyl  anilide, 

n  TT  /(I)  CO.NH.C6H5    .,          .     .     ,  u.  .      ,    . 

C6n4<r      (  ,  the    principal    product    obtained    is 


/(I)  CO.NH.C6H5 
C6H3^-(2)  OH 
\5)  N02 


The  nitro-anilides,  on  saponification,  by  heating  with  a 
concentrated  halogen  acid  or  with  caustic  soda,  yield  the  nitro- 
amido  compounds.  (To  obtain  the  nitro  compounds  by  the 
reduction  of  the  dinitro  derivatives,  see  under  Chapter  II.) 

The  carboxylic  acids  are  nitrated  less  easily.  Containing 
side-chains,  they  should  be  nitrated  cold,  or  by  using  a  less  con- 

1  For  the  production  of  the  nitro-dimethylanilines,  see  under  Chapter  I. 


SUBSTITUTIONS.  87 

centrated  acid.  The  oxy-carboxylic  acids,  like  the  acid  phenols, 
are  nitrated  very  readily;  salicylic  acid,  with  fuming  nitric 
acid,  immediately  gives  a  dinitro  acid;  to  obtain  the  mono- 
nitrated  acid,  it  is  necessary  to  dilute  the  nitric  acid  with  glacial 
acetic  acid.  The  aldehydes  and  ketones  require  to  be  cooled 
considerably;  they  are  nitrated  by  using  a  mixture  of  nitric  and 
sulphuric  acids.  Quinoline  and  its  derivatives  only  have  the 
hydrogen  of  the  benzene  nucleus  replaced,  and  not  that  of  the 
pyridine,  by  the  action  of  nitric  acid. 

The  formation  of  nitric  esters  by  the  action  of  nitric  acid 
on  alcohols  gives  rise  to  the  substitution  of  the  hydrogen  in 
hydroxyl  by  N02.  Though  frequent  in  the  aliphatic  series, 
this  reaction  is  rare  in  the  aromatic  compounds.  The  nitric 
acid  used  has  a  density  of  1.3  to  1.4,  and  is  deprived  of  its 
nitrous  vapors  by  urea;  it  is  cooled  and  mixed  with  the  alco- 
hol. The  ester  formed  is  separated  by  distillation  or  addition 
of  water.  If  the  alcohol  reacts  with  difficulty,  heat  is  used,  or 
sulphuric  acid.  It  is  necessary  to  avoid  the  formation  of 
reddish-brown  nitrous  fumes.  Many  oxy-acids  behave  in  the 
same  manner  as  the  alcohols.*  Among  the  aromatic  alcohols, 
the  only  one  which  yields  a  nitric  acid  ester  is  para-nitro- 
benzyl  alcohol: 


CH2.O.N02.0 


Replacement  of  NH2  by  N02. — This  can  be  brought  about 
by  the  use  of  the  diazo  compounds,  for  which  purpose  the 
nitrous  salts  are  treated  with  copper  suboxide.  For  example, 
the  nitrite  of  diazo-benzene,  C6H5N  :N.O.NO,  gives  nitro- 
benzene, C6H5.N02,  with  liberation  of  N2.  The  amido  com- 
pound is  dissolved  in  two  molecules  of  nitric  acid,  or  in  one 
molecule  of  dilute  sulphuric  acid;  and  there  is  added  one  mole- 
cule of  alkaline  nitrite,  then  a  second  molecule  to  form  the 


88  ORGANIC  SYNTHESES. 

salt.  To  the  solution  is  now  added  some  copper  suboxide; 
there  is  a  disengagement  of  nitrogen  and  a  formation  of  the 
nitro  compound. 

Substitution  of  a  halogen  by  an  N02  Group. — This  is  about 
the  only  method  of  obtaining  the  nitro  derivatives  of  the  ali- 
phatic series,  and  it  is  effected  by  allowing  CnH2n+iI  to  react 
with  AgN02  or  KN02.  However,  it  cannot  as  yet  be  affirmed 
with  certainty  that  the  compounds  obtained  are  true  nitro 
derivatives.1  These  are  not  the  only  bodies  formed,  however, 
as  simultaneously  there  are  always  produced  more  or  less  iso- 
meric  nitrous  esters.2  The  more  hydrogen  there  is  attached 
to  the  carbon  atom  holding  the  iodine,  the  less  will  be  the 
quantity  of  nitrous  ester  produced;  thus,  methyl  iodide, 
CHsI,  furnishes  only  nitro-me thane.  Ethyl  iodide  gives  partly 
nitrous  ester  and  partly  ni tro-e thane ;  and,  finally,  tertiary 
isobutyl  iodide,  (CHs^CI,  forms  only  a  small  quantity  of 
nitro-butane.  In  certain  cases  the  unsaturated  hydrocar- 
bons are  produced  as  secondary  products,  as  in  the  reaction 
of  silver  nitrite  on  secondary  butyl  iodide,  CH3.CH2.CHI.CH3, 
where  butylene  is  disengaged.  It  is  very  seldom  that  iodine 
compounds  are  distinguished  from  those  of  bromine.  The  reac- 
tion, especially  at  the  beginning,  takes  place  with  much  energy , 
so  that  it  is  prudent  to  introduce  the  silver  nitrite  in  small 
quantities  at  a  time,  and  to  keep  the  vessel  containing  the 
mixture  well  cooled.  Under  these  conditions  about  66  per 
cent  of  nitro-ethane  can  be  obtained.3 

The  separation  of  the  nitro  derivatives  and  the  isomeric 
nitrous  esters  offers  no  great  difficulty,  the  latter  being  the 
more  volatile.  They  may  also  be  separated  by  the  addition 
of  alcoholic  soda;  for  the  nitro  compounds,  with  the  excep- 
tion of  the  tertiary  ones,  form  sodium  compounds  which  are 

1  See  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  18,  p.  385. 

2  In  this  there  is  a  difference  between  the  reactions  RI-|-]VINO2  and  that  of 
HI4-MS03H;    for,  in  the  latter  case,  sulphonic  acids  are  almost  exclusively  ob- 
tained, without  the    formation  of   isomeric  esters,  as  in  the  case  of   the  nitro 
derivatives. 

9  See  Jour.  Soc.  Phys.  Chim.  Eusse,  vol.  14,  p.  227, 


SUBSTITUTIONS.  89 

difficultly  soluble.  During  the  reaction  of  iodo-ethyl  alcohol, 
CH2.LCH2.OH,  with  silver  nitrite,  there  is  formed  some  nitro- 
ethyl  alcohol,  CH2.N02.CH2.OH.  But  iodo-ethylene  and  chlor- 
iodo-ethylene  do  not  react  completely  with  silver  nitrite,  and 
dinitro  compounds  are  not  produced. 

The  dinitro  compounds  are  formed  by  the  action  of  potas- 
sium nitrite  on  brom-nitro  derivatives.  For  example,  to  the 
alcoholic  solution  of  brom-nitro-e thane,  CH3.CHBr.N02,  there 
is  added  an  aqueous  solution  of  potassium  nitrite,  and  then, 
an  alcoholic  solution  of  alkali;  there  is  formed  the  body 
CH3.CK(N02)2,  which,  on  treatment  with  sulphuric  acid,  gives 
dinitro-ethane,  CH3.CH(N02)2. 

Some  of  the  nitro  compounds  are  seemingly  obtained  by 
the  action  of  nitric  acid  on  the  substituted  aceto-acetic  esters, 
and  on  secondary  alcohols  (isopropyl  alcohol  excepted).  Some 
chemists  do  not  consider  these  bodies  as  nitro  compounds, 
but  as  nitrous  esters  of  dihydrates.  Thus  the  nitre-propane 
compound,  CH3.CH2.CH(N02)2,  is  given  the  formula 
CH3.CH2.CH(ONO)2.  The  formation  of  the  potassium  salts- 
(yellow  crystals)  of  the  dinitro  compounds,  or  nitrous  acid 
esters,  is  a  characteristic  reaction  for  secondary  alcohols.1 

lodo-benzene,  CeHsI,  with  silver  nitrite,  reacts  when  heated 
for  a  long  time,  and  gives  nitro  derivatives  of  phenol.  With 
benzyl  iodide,  CeHsCHJ,  there  is  formed  benzaldehyde,  benzoic- 
acid,  and  nitrous  oxide,  NO. 

In  certain  cases  the  halogen  of  carboxylic  acids  can 
also  be  replaced  by  N02.  Thus  brom-ethyl  acetate,. 
CH2Br.CO.OC2H5,  with  silver  nitrite,  gives  ethyl  nitro- 
acetate,  CH2N02.CO.OC2H5;  even  /9-brom-propionic  acirl, 
CH2.Br.CH2CO.OH,  is  converted  into  /?-nitro-propionic  acid. 
With  chlor-acetic  acid,  CH2C1.CO.OH,  and  potassium  nitrite, 
in  place  of  nitro-acetic  acid,  there  are  produced  decompo- 
sition products  of  CH3N02  and  C02. 

Substitution  of  a  halogen  by  O.NO. — Formation  of  nitrous 
esters  from  RI  and  MN02.  (See  page  88.) 

1  This  is  Chancel's  reaction.     See  Bull.  Soc.  Chim.,  vol.  31,  p.  504,  and  Compt. 
rend.,  vol.  100,  p.  604. 


9°  ORGANIC  SYNTHESES. 

Substitution  of  a  halogen  by  O.N02.  —  Formation  of  nitric 
esters  by  the  action  of  silver  nitrate  on  halogen  compounds. 
The  nitric  ester  of  allyl  alcohol  is  obtained  according  to  the 
following  reaction: 

CH2  :  CH.CH2  Br  +  AgO.N02  =  CH2  :  CH.CH2.O.N02  +  AgBr. 


NO 


C 


with  silver  nitrate,  gives  C64. 

Substitution  of  H2  by  >N.OH.  —  When  nitrous  acid  acts 
on  bodies  which  contain  a  CH2  group  (adj  oining  negative  groups 
such  as  CO  or  N02),  the  following  reaction  takes  place: 

R2.CH2  +  NO.OH  =  H20  +  R2.C  :  N.OH; 
and  isonitro  compounds  are  formed,  thus: 

CO.O.C2H5  CO.OC2H5 

H2  +NO.OH  =  H20+C  =  N.OH  $ 

CO.O.C2H5  CO.OC2H5 

CO.CH3  CO.CH3 

CH2  +NO.OH  =  H20+C=N.OH 

CO.OC2H5  CO.OC2H5 

In  order  to  obtain  isonitroso-malonic  ester,  N20a  is  passed 
into  a  mixture  of  malonic  ester  and  sodium  alcoholate  until 
no  further  absorption  takes  place;  the  isonitroso  compound 
is  separated  by  the  addition  of  water.  In  order  to  obtain  iso- 
nitroso-aceto-acetic  ester,  potassium  nitrite  is  added  to  a  solu- 
tion of  aceto-acetic  ester  in  an  alkaline  alcoholic  mixture,  while 
it  is  well  cooled,  and  then  20  per  cent,  sulphuric  acid  is  run  in. 
After  the  reaction  is  completed  the  liquid  is  made  alkaline, 
and  any  unchanged  aceto-acetic  ester  is  removed  by  ether; 
on  acidifying  again,  the  isonitroso  compound  is  separated. 


SUBSTITUTIONS.  91 

Benzyl  cyanide,  C6H5.CH2.CN,  with  amyl  nitrite  in  the  pres- 
ence of  alcohol,  is  also  converted  into  an  isonitroso  compound, 


The  substituted  aceto-acetic  esters  of  the  general  formula 
CH3.CO.CHR.CO.OC2H5, 

during  their  transformation  into  isonitroso  compounds,  are 
saponified  at  the  same  time,  and  the  final  reaction  may  be, 
expressed  thus: 

/riTT 

Ha-COXK^pJL       +|H|+|0|N.OH 


|CQ.O|C2H5     OH| 

CH3 

I 
= CH3CO  .C :  N.OH  + C02 + C2H5.OH 

'  The  isonitroso  ketones  may  be  obtained  by  treating  ketones 
with  amyl  nitrite  in  the  presence  of  hydrochloric  acid  or  sodium 
ethylate. 

Primary  nitro  compounds  (or  rather  their  metallic  salts) 
are  converted  into  nitrolic  acid  derivatives  (the  salts)  by 
nitrous  acid.  It  is  supposed  that  H2is  exchanged  for  >N.OH. 


R.CH2.N02  -->    R 

Nitrolic  acid. 

During  the  formation  of  diazo  compounds,  there  also  occurs 
the  substitution  of  H2  (of  the  amido  group)  by  >N.OH  (or 
>NC1,  >N.N03,  etc.). 

Substitution  of  a  halogen  by  N.OH  takes  place  in  the 
action  of  hydroxylamine  on  compounds  which  contain  two 
atoms  of  halogen  attached  to  a  single  carbon  atom.  Dibrom- 
nitro-e thane,  CH3.CBr2.N02,  is  presumably  converted  into  ethyl 
nitrolic  acid, 

p/N.OH       f. 

'C\N02       (?) 


92  ORGANIC  SYNTHESES. 

The  halogen  substitution  products  of  ketones  behave  in 
the  same  manner;  but  their  oxygen  also  reacts  with  hydroxyl- 
amine  and  produces  oximido  ketoximes; 


CO       +2H2N.OH=C:N.OH      +H20+2HC1. 
CH.C12  CHrN.OH 

Substitution  of  0  by  N.OH.  —  Aldehydes  and  ketones,  as  well 
as  quinones,  replace  the  0  by  N.OH  by  the  action  of  hydroxyl- 
amine  in  aqueous  or  alcoholic  solution,  giving  rise  to  aldoximes, 
ketoximes,  and  quinone-oximes.  The  reaction  proceeds  tran- 
quilly in  the  cold  by  leaving  the  two  bodies  in  contact.  It  is 
more  convenient  to  use  a  solution  of  hydroxylamine  hydro- 
•chloride  (the  presence  of  ammonium  chloride  is  not  injurious) 
iwdth  the  theoretical  quantity  of  sodium  carbonate. 

Ketonic  or  aldehydic  acids  and  their  esters  readily  react 
with  hydroxylamine.  Bodies  which  contain  two  CHO  or  CO 
groups  react  with  two  and  sometimes  with  only  one  molecule 
of  hydroxylamine.  Glyoxal  gives  glyoxime: 


CHO  CH:N.OH 

+2H2N.OH=|  +  2H20. 

HO  CH:N.OH 


X-', 

A 


N.OH 

The  oxime  obtained  with  anthraquinone,  CeEU  /U 


CO  /CeH4r 


does  not  react  any  further  with  hydroxylamine,  while  its  isomer, 
prepared  with  phenanthraquinone,  reacts  at  180°  C.  with 
another  molecule  of  hydroxylamine,  giving  the  dioxime  or  its 
anhydride : 

C6H4.C:N.OH  C6H4.C:N.OH 

>   |         |  

O  C6H4.C:N.OH 


SUBSTITUTIONS.  93 

The  oxime,  which  corresponds  to  benzoquinone,  and  which 
is  para-nitroso-phenol,  obtained  by  the  action  of  hydroxyl- 
-amine  on  quinone,  reacts  with  another  molecule,  giving  quinone- 
dioxime,  C6H4(N.OH)2. 


E.  Preparation    of   Ammonia   Derivatives. 

Substitution  of  a  halogen  by  NH2. — In  the  aliphatic  series, 
and  in  the  side-chains  of  the  aromatic  series,  this  takes  place 
through  the  action  of  ammonia  on  the  halogen  esters.  How- 
ever, the  reaction  cannot  be  expressed  by  the  simple  equation 
RI  +  2NH3  =  RNH2+NH3.HI,  because,  besides  the  primary 
amines,  there  are  also  produced  secondary  amines,  according  to 
the  time,  the  temperature,  and  the  mass  of  the  reacting  bodies.1 

It  is  also  necessary  to  take  into  consideration  whether 
aqueous  or  alcoholic  solutions  of  ammonia  are  used,  and  also 
the  character  of  the  halogen  compounds.  In  the  case  of 
primary  compounds,  there  are  formed  not  only  tertiary  amines 
but  also  ammonium  derivatives;  in  the  case  of  secondary 
bodies,  the  chief  product  consists  of  primary  bases.  The 
tertiary  iodides  react  with  ammonia  but  do  not  give  amines; 
they  are  decomposed  with  the  formation  of  unsaturated  hydro- 
carbons.2 The  reaction  is  carried  out  in  sealed  tubes  at  100°  C.3 

The  separation  of  the  primary  amines  from  the  products 
formed  with  them  is  sometimes  very  difficult.  With  the 
lower  homologues,  recourse  cannot  be  had  to  distillation,  as 
the  difference  between  the  boiling-points  of  the  primary, 
secondary,  and  tertiary  amines  is  too  small.  Generally, 
recourse  is  had  to  the  oxalic  esters.  The  product  of  the  reaction 

1  According  to  some,  these  bodies  are  formed  successively;  and,  as  there  is 
always  an  excess  of  ammonia,  the  free  bases  are  produced,  their  alkalinity  being 
more  feeble  than  that  of  ammonia,  which  decomposes  their  salts. 

2  Also,  during  the  reaction  of  secondary  iodides  with  ammonia  and  the  amines, 
the  unsaturated  hydrocarbons  are  readily  formed.      Isopropyl  iodide,  (CH3)2CHI, 
with  isopropylamine,  (CH3)2CH.NH2,  gives  propylene,  CH3.CH  :CH2.) 

3  Methylamine  can  be  formed  at  the  ordinary  temperature  by  liquefying  a 
mixture  of  methyl  chloride  and  ammonia. 


94  ORGANIC  SYNTHESES. 

is  evaporated  on  a  water-bath,  then  potash  is  added  to  the 
mixture  of  the  salts,  and  on  distillation  the  ammonium  com- 
pound, is  left  behind,  as  it  is  not  decomposed  by  potash.  The 
distillate  consists  of  the  amines  R.NH2,  R2.NH,  and  R3.N, 
This  mixture  of  amines  is  then  treated  by  the  oxalic  ester 
method. 

The  aromatic  amines  may  be  separated  by  the  fractional 
crystallization  of  their  salts;  the  salts  of  the  secondary  amines 
are  less  soluble  than  those  of  the  primary,  and  more  so  than 
those  of  the  tertiary.  Also  the  difference  in  basicity  is  utilized, 
and  the  separation  may  be  accomplished  by  means  of  acids. 
Thus,  a  mixture  of  benzylamines,  taken  up  with  a  small  quan- 
tity of  dilute  hydrochloric  acid,  will  give  up  at  first  the  mono- 
and  di-benzylamines,  (C6H5.CH2)  .NH2  and  (C6H5.CH2)2.NHr 
and  these  may  be  separated  subsequently  by  crystallization; 
the  residue  will  be  the  tertiary  amine,  (C6H5.CH2)3.N. 

The  halogen  of  chlorhydrins,  (CH2.C1.CH2OH),  as  well  as 
the  substitution  products  of  the  carboxylic  acids,  may  also 
be  replaced  by  NH2.  The  ester  of  chlor-formic  acid,  C1CO.OR, 
with  ammonia,  gives  carbamic  acid,  NH2CO.OR.  The  esters 
of  other  chlor-acids  behave  in  a  slightly  different  manner; 
they  are  converted  into  chlor-acid  amides.  With  chlor-ethyl 

CH2C1  CH2C1 

acetate,  ,  there  is  formed  chlor-acetamide,    |  > 

CO.OC2H5  CO.NH2 

which,  heated  with  ammonia,  has  the  chlorine  replaced  to  give 
amido-acetamide,  NH2CH2.CO.NH2.  For  the  preparation  of 
similar  amines,  heating  with  lead  hydrate  is  employed;  the 
lead  salt  thus  obtained  is  decomposed  by  means  of  hydrogen 
sulphide. 

The  other  esters  of  the  inorganic  acids  behave  in  the  same 
manner  as  the  halogen  compounds. 

In  the  aromatic  nucleus  the  halogen  is  seldom  replaced  by 
the  amido  group  by  treatment  with  ammonia.  Brom-nitro- 

benzene,    CeH^  L)  Br  *'   and     similarly    chlor-nitrobenzene, 


SUBSTITUTIONS.  95 


,  heated  in  sealed  tubes  at  180°  C.  with  am- 

monia, give  ni  tramline;  but  the  meta-brom-nitrobenzene 
scarcely  reacts  at  all  with  ammonia.  In  chlor-dinitrobenzene, 

/(I)  Cl 
C6H3(—  (2)  N02,  the    chlorine   is   replaced   by   simply   boiling 

\(4)  N02 

with  ammonia  water.  The  corresponding  bromine  compound 
reacts  with  difficulty,  and  the  iodine  compound  is  even  less 
reactive.  If  two  N02  groups  are  found  in  the  ortho  posi- 
tion to  one  another,  one  of  the  two  can  be  replaced  by  NH2. 

/(I)  Cl 

Thus  chlor-dinitrobenzene,  C6H3^-(3)  N02,  is   converted  into 

\(4)  N02 

/(I)  Cl 

chlor-nitrotoluidine,  C6H3^(3)  NH2. 

\(4)  N02 

The  substitution  of  halogens  by  NH2  takes  place  easily 
by  the  action  of  aqueous  or  gaseous  ammonia  on  the  chlorides 
of  the  carboxylic  acids.  The  reaction  takes  place  in  the  cold 
and  gives  very  good  yields.  In  the  aliphatic  series  there  is 
also  formed  a  secondary  amine  as  a  by-product.  In  carrying 
out  the  reaction,  the  acid  and  phosphorus  trichloride  are  taken, 
and  not  the  ready-prepared  chloride. 

By  cautiously  treating  with  ammonia  such  compounds  as 
dichlor-propionyl  chloride,  CH3.CC12.CO.C1,  the  chlorine  is  only 
replaced  in  the  COC1  group. 

The  chlorides  of  the  sul  phonic  acids  react  with  difficulty; 
their  amides  can  be  prepared,  nevertheless,  by  using  gaseous 
ammonia  dissolved  in  ether,  and,  less  readily,  by  prolonged 
boiling  with  aqueous  ammonia. 

Substitution  of  OH  by  NH2.  —  This  can  only  be  effected  by 
heating  with  ammonia  or  its  salts  in  sealed  tubes,  with  or 
without  dehydrating  agents.  With  the  aliphatic  alcohols 
there  are  formed  primary,  secondary,  and  tertiary  amines, 
and  often,  as  by-products,  unsaturated  hydrocarbons.  One 
may  conveniently  use  the  ammoniacal  chloride  of  zinc,  which 


$  ORGANIC  SYNTHESES. 

is  prepared  by  passing  ammonia  over  powdered  zinc  chloride 
heated  to  300°  C.  The  latter  absorbs  four  times  its  weight 
of  ammonia.  The  body  R.OH  is  heated  for  fifteen  hours  at 
250°  C.  with  the  ammoniacal  chloride.  The  yield  is  from  50  to 
75  per  cent,  of  the  weight  of  the  alcohol  used  in  the  reaction. 
The  reaction  with  phenols  takes  place  more  readily.  /3-naph- 
thylamine,  with  a  certain  quantity  of  /?-dinaphthylamine,  is 
obtained  by  passing  dry  ammonia  over  /?-naphthol  strongly 
lieated.  Anthrol  gives  anthramine: 


/\  /x 

C6H4  C6H3.OH    --  >    C6H4     |        C6H3.NH 


When  heated  to  200°  C.  with  aqueous  ammonia,  alizarin 
is  converted  into  diamido  anthraquinone.  Many  of  the  nitro- 
phenols  also  react  readily  with  ammonia  in  concentrated  solu- 
tion. With  other  phenols,  ordinary  phenol  for  example,  it  is 
necessary  to  heat  with  ammoniacal  chlorides  of  zinc  or  cal- 
cium at  elevated  temperatures.  One  part  of  the  phenol  remains 
unattacked;  but  it  is  easy  to  separate  this  from  R.NH2  by 
the  aid  of  acids  and  alkalies. 

The  cyan-hydrins  (produced  by  the  combination  of  hydro- 
cyanic acid  with  aldehydes  and  ketones)  react  with  ammonia 
with  remarkable  ease,  and  give  the  nitriles  of  the  a-amidocar- 
boxylic  acids.  Thus: 

CH3\p  /OH     NH      CH3\r/NH2    H  0 

H/(\CNH'NH3=   H/°\CN 

The  latter  body,  on  saponification,  gives  amido-propionic  acid 
or  alanine. 

The  acids  of  the  aliphatic  series  have  their  OH  replaced  by 
NH2,  and  are  converted  into  amides,  when  they  are  treated 
with  ammonium  sulphocyanide,  CNS.NH4: 

2CH3.CO.OH  +  CNS.NH4  =  2CH3.CO.NH2  +  COS  +  H20. 


SUBSTITUTIONS. 


97 


There  is  generally  formed  a  certain  quantity  of  nitrile  as  a 
secondary  product. 

Substitution  of  OH  by  NH.R  and  NR2.— This  is  accom- 
plished by  heating  phenolic  bodies  with  primary  and  secondary 
amines,  NH2.R  and  NH.R2.  The  reaction  is  sometimes  more 
easily  brought  about  than  with  ammonia.  Thus  aurine  is 
more  readily  converted  into  trimethyl-rosaniline  than  into 
Tosaniline : 


/C6H4.OH 
C^-C6H4.OH 
\C6H4.0 


/C6H4.NH.CH3 
A}6H4.NH.CH3 
\C6H4.NH.CH3.C1 


Aurine. 


Hofmann'a  violet. 


a-  and  /?-naphthols  are  converted  into  monomethyl  a-  and 
/?-naphthylamines  by  the  action  of  monomethylamine. 

Fluorescein  heated  with  dimethylamine  gives  tetra- 
methyl-diamido-fluorescein,  or  rhodamine,  a  magnificent  red 
dyestuff : 


OH 


(CH3)2N 


N(CH3)2 


Fluorescein. 


Rhodamine. 


These  cases  can  be  considered  as  indirect  condensations 
with  disengagement  of  water. 

Substitution  of  O  by  NH. — This  is  brought  about  in  cer- 
tain cases  by  the  action  of  ammonia.  Thus,  different  deriv- 
atives of  pyrone,  C5H402,  heated  with  ammonia,  and  some- 
times even  at  the  ordinary  temperature,  are  converted  into 
pyridone  derivatives,  C5H4O.NH.  The  acid  C5H302,  CO.OH, 


ORGANIC  SYNTHESES. 


forms   C5H40.N.CO  :  OH.    The    following    formulas    represent 
pyrone  and  pyridone: 


As  derivatives  of  pyrone,  there  are,  among  others,  meconia 
acid,  chelidonic  acid,  which  is  tribasic,  and  pyromeconic  acid, 
which  probably  does  not  contain  a  carboxyl  group,  but  which. 
should  be  hydroxy  pyrone,  C5H3(OH)02. 

On  heating  fluorescein  with  ammonia  there  is  substituted 
not  only  OH  by  NH2,  but  also  0  by  NH.  The  following 
formulas  for  these  bodies  have  been  given: 


OH  OH  NH2          NH 


Fluorescein.  Diamido-imido-fluorescein. 


Substitution  of  S  by  NH.—  When  sulphur  is  attached  to 
a  carbon  atom  with  two  bonds,  it  may  be  replaced  by  NH 
by  the  action  of  ammonia.  This  reaction  generally  takes  place 
only  in  the  presence  of  substances  reacting  with  the  hydrogen 
sulphide  liberated,  such  as  the  oxides  of  lead  or  mercury. 
Thus,  from  the  thio-ureas  are  formed  the  guanidines: 


SO\NHC6H5+NH3+Pb0=C=NH 

\NH 


The  thio-amides  react  in  the  same  manner  with  ammonia 
in  the  presence  of  mercuric  chloride. 


SUBSTITUTIONS.  99 

P.  Methods  for  Obtaining  Thio  and  Sulpho    Compounds,  and 
the  Acid  Esters  of  Sulphuric  Acid. 

Substitution  of  0  by  S.— The  pentasulphide  of  phosphorus 
is  generally  employed,  but  in  the  CO  group  the  0  is  also  replaced 
by  the  action  of  hydrogen  sulphide,  aldehydes  and  ketones 
being  thus  converted  into  thio  compounds. 

Benzophenone,  (C6H5)2CO  at  100°,  with  phosphorus  penta- 
sulphide, P2S5,  or  with  an  alcoholic  solution  of  ammonium 
sulphydrate,  gives  the  mercaptan  ((C6H5)2C(SH)2. 

Amides  are  converted  into  thio-amides  by  phosphorus 
pentasulphide;  but  as  the  reaction  is  very  energetic,  and  as 
there  may  be  a  liberation  of  hydrogen  sulphide  and  the  for- 
mation of  nitriles,  it  is  better  to  use  the  anilides.  Thus,  for- 
manilide,  C6H5.NH.CHO,  heated  on  a  water-bath  with  P2S5, 
gives  C6H5.NH.CSH. 

The  cyanates,  by  the  action  of  phosphorus  pentasulphide, 
give  sulphocyanides.  The  0  of  the  OH  group  is  replaced 
by  S  only  by  the  use  of  P2S5.  Acetic  acid  gives  thio  acetic 
acid. 

With  phenols,  besides  mercaptans,  phosphorus  pentasul- 
phide also  gives  esters  of  phosphoric  acid.  For  example: 

8C6H5.OH  +  P2S5  -  2[PO(OC6H5)  3]  +  3H2S  +  2C6H5.SH. 

For  a  description  of  the  methods  of  replacing  0  by  the 
aid  of  P2S3,  see  previous  pages. 

Substitution  of  halogens  by  S. — The  metallic  sulphides 
are  used  for  this  purpose.  Thus: 

2CH3I +R2S  =  (CH3)2S +2RI. 

But  the  products  resulting  from  the  action  of  phosphorus 
pentachloride  on  anilides  may  be  converted  into  thio-anilides 
by  the  action  of  hydrogen  sulphide  (thus,  the  compound 
eHs  is  converted  into  thio-benzanilide) . 


100  ORGANIC  SYNTHESES. 

Substitution  of  halogens  by  HS.  —  This  is  accomplished  by 
heating  the  halogen  with  an  aqueous  or  alcoholic  solution  of 
potassium  sulphydrate: 

C2H5Br  +  KSH  =  C2H5.SH  +  KBr. 

Sometimes,  with  mercaptans,  other  sulphur  compounds  are 
obtained,  according  to  the  equation: 

2RC1  +  2KSH  =  R2S  +  H2S  +  2KC1. 

The  chlorides  of  the  carboxyl  and  sulphonic  acids  behave  in 
the  same  manner  with  potassium  sulphydrate.  The  halogen 
to  be  found  in  the  aromatic  nucleus  is  replaced  by  HS  under 
the  same  conditions  under  which  the  OH  group  is  replaced 

/(I)  .Cl 
by   NH2.    Thus,  nitro-dichlor-benzene,  C6H3^-(2)  N02,  with 

\(4)  Cl 
/(I)  SH 
ammonium  sulphide,  givesCeH3^-(2)  N02. 

\(4)  Cl 

Substitution  of  NH2  by  HS.  —  In  certain  cases  this  can  be 
realized  by  the  aid  of  the  diazo  compounds.  In  fact,  if  ta 

/N  v 
diazo-benzene  sulphonic  acid,  C6HX          /N,  there  is  added 


an  alcoholic  solution  of  potassium  sulphide,  a  liberal  disengage- 

XSK 
mentof  nitrogen  takes  place,  and  there  is  formed  C6H4<^  OQ  TT-J- 

the  reaction  also  gives  rise  to  the  formation  of  various  secondary 
products. 

Substitution   of  NH  by  S.  —  This  is  brought  about  by  the 


direct  action  of  hydrogen  sulphide;  thus,     65.x    -     * 


heated  with  hydrogen  sulphide  to  130°  C,  is  converted  into 


SUBS  TITUTIONS.  '  ',  i  £E 

The  reaction  takes  place  better  on  heating  amidines  in  a  sealed 
tube  with  carbon  disulphide: 


In  the  same  manner  the  group  N.R  can  also  be  replaced  by  S. 

Substitution  of  H  by  SO2.OH.  —  This  may  be  accomplished 
by  the  action  of  concentrated  or  fuming  sulphuric  acid,  of  the 
anhydride,  or  of  chlorsulphonic  acid,  S02(OH)C1.  The  mono- 
sulphonic  acids  of  the  aromatic  hydrocarbons  are  obtained 
by  treating  the  latter  in  the  cold,  and  more  rapidly  by  heat- 
ing with  concentrated  sulphuric  acid.  With  chlorsulphonic^ 
acid,  it  is  necessary  to  operate  cold,  or  even  with  artificial 
refrigeration. 

The  insoluble  sulphonic  acids  are  separated  by  the  addition 
of  a  little  water;  they  may  be  recrystallized  from  sulphuric 
acid  not  too  dilute.  For  the  soluble  acids  the  acid  liquor  is 
diluted  with  water  and  saturated  with  carbonate  of  lead  or 
barium,  and  the  salts  are  purified  by  crystallization,  after 
having  removed  the  insoluble  sulphate  by_  filtration^  The  salt 
is  then  decomposed  with  sulphuric  acid  or  hydrogen  sulphide. 
In  order  to  separate  the  isomers,  it  is  best  to  form  the  chlorides 
by  treating  with  phosphorus  pentachloride,  and  then  the 
amides  by  the  action  of  ammonia.  After  crystallization  of 
the  amides,  the  acids  are  set  free  by  heating  under  pressure 
with  hydrochloric  acid. 

For  compounds  containing  several  sulphonic  acid  groupsr 
it  is  better  to  use  fuming  sulphuric  acid  and  heat,  or,  still  bet- 
ter, to  pass  the  vapors  of  the  hydrocarbon  into  acid  of  66°  Be, 
heated. 

The  anhydride,  S03,  and  chlorsulphonic  acid,  S02(OH)Clr 
at  an  elevated  temperature,  can  give  rise  to  sulphones;  these 
are  easily  separated,  owing  to  their  insolubility  in  water. 

The  halogen  and  nitro  substitution  products  of  the  aromatic 
hydrocarbons  behave  with  sulphuric  acid  like  the  hydrocar- 


;    ORGANIC  SYNTHESES. 

bons  themselves.  (Bodies  containing  a  halogen  in  the  side- 
chain  are  carbonized  with  sulphuric  acid.)  Certain  bromine  and 
iodine  compounds  give  with  sulphuric  acids  certain  higher  halo- 
gen substitution  products.  Thus,  dibrom-benzene,  CeH^  W  5r, 

gives  tetrabrom-  and  hexabrombenzenes.1 

The  amido  compounds  readily  yield  sulphonic  acids  on 
heating  their  sulphates,  at  180-200°  C,  either  simple  or  alco- 
holated,  until  water  or  alcohol  is  no  longer  set  free.2  Thus: 

C6H5.NH2.S04H2=C6H4/^  s5H  +  H2°' 

^(2)NH32     +C2H5.OH. 
\(5)  S02OH 

Both  processes  give  good  yields  of  the  sulphonic  acids.3 

A  particular  case  for  obtaining  the  amido-sulphonic  acids 
consists  in  the  action  of  ammonium  hydrosulphide  on  the 
nitro  compounds,  a-nitro-naphthalene  is  converted  into  the 
ammonium  salt  of  amido-naphthalene-sulphonic  acid. 

The  temperature  is  of  great  importance  in  the  production 
of  different  isomers,  particularly  with  the  phenol  sulphonic 
acids.  Chlorsulphonic  acid  may  be  employed,  acting  on  a 
solution  of  phenol  in  carbon  disulphide. 

The  carboxylic  acids  of  the  alphatic  series  are  converted 
into  sulphonic  acids  by  the  anhydride,  S03,  or  chlorsulphonic 
acid;  in  the  aromatic  series,  fuming  sulphuric  acid  is  necessary, 
and  also  high  temperatures. 

Sulphuric  acid  reacts  with  difficulty  on  the  pyridine  nucleus. 
With  pyridine  it  is  necessary  to  heat  to  320°  C.  Also  quinoline 

1  The  acid  plays  the  part  of  the  brominating  agent.      See  Berichte,  vol.  25, 
P.  1526. 

2  The  action  of  sulphuric  anhydride  on  the  aliphatic  amines  is  to  form  sul- 

phaminic  acids:   C2H5.NH2+SO3=SO2<^§  c  H  . 

3  The  sulphovinic  esters  of  the  amido  compounds  are  obtained  by  the  double 
decomposition  of  the  calcium  salts  with  oxalates  of  the  bases. 


SUBSTITUTIONS.  103 

gives  a  sulphonic  acid  in  the  benzene  nucleus,  but  not  in  the 
quinoline  part  of  the  molecule. 

The  saturated  hydrocarbons  and  their  halogen  substitu- 
tion products  do  not  react  with  sulphuric  acid.  The  satu- 
rated alcohols,  however,  react;  methyl  alcohol  with  fuming 
sulphuric  acid  gives  CH2(OH)S03H  and  CH(OH)(S03H)2. 
The  anhydride,  S03,  gives  similar  bodies  by  uniting,  not  with 
the  carbon  attached  to  the  OH  (except  with  CH3.OH),  but 
with  the  neighboring  atom: 


The  amides  and  the  nitriles,  at  the  same  time  they  are 
saponified,  are  also  converted  into  sulphonic  acids.  Aceto- 
nitrile  gives  sulphacetic  acid,  which  in  its  turn,  under  the  influ- 
ence of  sulphuric  acid,  is  decomposed  with  liberation  of  car- 
bonic acid  and  the  formation  of  the  disulphonic  acid  of  methane  : 

CH3.CN  +  3S04H2  =  CH2(S03H)  2  +  C02  +  S02(OH)  (O.N  H4)  . 

Substitution  of  halogens  by  S02.OH.  —  This  is  an  indirect 
way  of  obtaining  the  sulphonic  acids  of  the  aliphatic  series. 
This  reaction  takes  place  by  the  action  of  sulphites  on  halogen 
compounds  : 

CH2.C1  CH2.S03.Na 

|  +S03Na2=  +NaCL 

CO.OM  CO.OM 

The  ammonium  salt  may  also  be  used.  If  ethyl  iodide  is 
heated  with  an  aqueous  solution  of  ammonium  sulphite  until 
complete  dissolution,  with  ammonium  iodide,  there  is  formed 
at  the  same  time  C2H5.S03.NH4.  The  mixture  is  diluted 
with  water  and  boiled  with  lead  oxide  until  ammonia  ceases 
be  to  evolved  ;  and  after  filtering,  in  order  to  remove  the  iodide 
of  lead,  there  is  in  solution  the  lead  salt  of  the  sulphonic  acid, 
which  only  requires  to  be  decomposed  with  hydrogen  sulphide. 

If  there  is  in  the  compound  several  atoms  of  a  halogen, 


104  ORGANIC  SYNTHESES. 

these  may  be  substituted  totally  or  partially,  according  to  the 
quantity  of  the  salt  used  in  the  reaction.  There  may  also 
be  a  reduction  of  the  halogen. 

In  the  aromatic  compounds,  the  halogen  which  is  in  the 
side-chain  may  also  be  replaced: 

°*<(i)  CTiBr+K^'-^S!  CH,S03K+KBr- 

Brom-benzyl-bromide. 

In  derivatives  of  phenol,  quinone,  etc.,  it  is  only  partially 
replaced.  Thus,  trichlor-phenol  with  potassium  sulphite  gives 
dichlor-phenol-sulphonate  of  potassium  and  the  chlor-phenol- 
disulphonate. 

The  halogens  united  to  nitrogen  are  easily  replaced  by 
sulphuric  acid:  the  solution  of  the  chloride,  C6H4(OH)N:N.C1 
(obtained  by  the  addition  of  the  theoretical  quantity  of  so- 
dium nitrite  to  the  cooled  solution  of  the  hydrochloride  of 
ortho-amido-phenol),  treated  with  potassium  sulphite,  gives 


Substitution  of  NH2  by  SO3H.  —  This  offers  an  indirect 
means  of  obtaining  sulphonic  acid  derivatives,  and  is  effected 
by  passing  N203  into  a  concentrated  alcoholic  solution  of  the 
base,  saturated  with  sulphurous  acid  : 


The  diazo  bodies  behave  in  this  manner  on  boiling  with  an 
alcoholic  solution  of  sulphurous  acid. 

Substitution  of  OH  by  S04H.  —  In  the  aliphatic  series  this 
is  accomplished  as  readily  as  the  substitution  of  H  by  S03H 
in  the  aromatic  series: 

CH3.OH+S04H2  =  H20+CH3.O.S02.OH. 

Sulphuric  acid  reacts  so  energetically  with  the  alcohols 
that  it  is  necessary  to  mix  them  with  caution;  the  reaction  is 
finished  by  heating  for  a  time  on  a  water-bath.  On  diluting 


SUBSTITUTIONS.  105 

with  water,  the  excess  of  sulphuric  acid  is  removed,  as  already 
explained.  The  free  acids  are  obtained  very  easily  by  means 
of  the  lead  salts  which  are  decomposed  by  hydrogen  sulphide. 
The  acid  esters  of  sulphuric  acid  are  also  obtained  by  adding 
gradually  to  chlor-sulphonic  acid  the  theoretical  amount  of 
well-cooled  alcohol: 

C2H5.OH + S02.OH.C1  =  C2H5.O.S02.OH  +  HCI. 

The  acid  esters  of  the  phenols  are  in  general  very  unstable, 
and  cannot  be  prepared  by  the  action  of  sulphuric  acid 
on  phenols  (/?-naphthol-sulphate,  CioH7.O.S02.OH,  offers  an 
exception,  as  it  is  formed  by  the -direct  action  of  sulphuric 
acid).  In  order  to  prepare  the  corresponding  alkali  salts, 
potassium  pyrosulphate  is  added  to  the  concentrated  aqueous 
solution  of  the  alkali  phenate,  and  heated  for  several  hours 
at  60-70°  C.  The  following  equation  may  be  taken  as  repre- 
senting the  reaction: 

C6H5.OK  +  K2S20  7  =  C6H5.O.S02.OK  +  S04K2. 

If  higher  heat  is  used,  the  para-sulpho-phenol  is  formed. 

Substitution  of  H  by  S02C1. — This  is  accomplished  by  the 
action  of  sulphuryl  chloride,  S02C12,  on  the  alcohols  and 
secondary  amines.  By  gradually  adding  the  theoretical  quan- 
tity of  alcohol  to  sulphuryl  chloride  ~and  cooling,  an  energetic 
reaction  takes  place,  hydrochloric  acid  being  liberated,  while 
there  is  formed  RO.S02C1,  in  the  form  of  a  heavy  oil,  which  is 
purified  by  washing  with  cold  water  and  drying  over  potash. 
The  action  of  sulphuryl  chloride  on  the  hydrochloride  of 
dimethyl-amine  gives 

(CH3)2.N.S02C1. 

Substitution  of  S03H  by  OH. — (See  previous  pages.) 


106  ORGANIC  SYNTHESES. 


G.  Methods  for  the  Preparation  of  Metallo-Organic  Derivatives. 

The  substitution  of  H  by  a  metal  occurs  in  the  OH  (also 
in  SH),  CH2,  and  NH  groups.  The  hydrogen  of  alcoholic  OH 
is  replaced  by  the  action  of  the  alkali  metals,  and  also  (espe- 
cially with  the  polyatomic  alcohols)  by  the  action  of  the  oxides 
of  barium,  calcium,  and  lead. 

In  phenols  the  H  of  OH  is  replaced  by  the  action  of  alkali 
metals. 

In  acids,  the  hydrogen  is  readily  replaced  by  a  metal  by 
double  decomposition  with  the  salts.  In  order  to  prepare  the 
salts  of  potassium,  sodium,  calcium,  barium,  and  strontium, 
the  free  acid  is  saturated  by  the  corresponding  base.  The 
oxides  of  barium,  calcium,  and  strontium  may  be  used  in 
excess,  and  afterwards  removed  by  saturating  with  carbonic 
acid.  If  the  salt  is  not  soluble  in  alcohol,  it  may  be  precipitated 
from  its  aqueous  solution  by  the  addition  of  alcohol. 

The  salts  of  potassium  and  sodium  soluble  in  alcohol  .may 
be  prepared  by  saturating  the  alcoholic  solution  of  the  acid 
with  the  carbonates  of  potassium  or  sodium. 

The  salts  of  the  alkaline  earth  and  heavy  metals  may  be 
prepared  by  saturating  the  free  acid  with  oxides  of  these 
metals,  or  by  double  decomposition  of  the  alkaline  or  ammo- 
nium salts  with  barium  chloride,  acetate  of  lead,  sulphate  of 
copper,  nitrate  of  silver,  etc.  This  method  is  used  for  the 
preparation  of  insoluble  or  difficultly  soluble  salts.  The  silver 
salts  of  the  aromatic  acids  are  prepared  more  readily  by  double 
decomposition  of  the  calcium  salts  with  pure  silver  nitrate 
not  containing  any  free  acid. 

The  calcium,  barium,  and  lead  salts  are  often  prepared; 
in  order  to  obtain  the  free  acid  it  is  simply  sufficient  to  decom- 
pose these  salts  with  oxalic  acid,  sulphuric  acid,  or  hydrogen 
sulphide,  after  having  purified  them  by  crystallization.  The 
silver  salts,  not  containing  any  water  of  crystallization,  serve 
especially  well  for  the  determination  of  the  molecular  weights 


SUBSTITUTIONS  107 

<r 

of  the  acids;  ignited  at  a  red  heat,  they  leave  pure  silver,  with 
the  exception  of  cuminic  acid,  which  leaves  a  carbide  of  silver. 

To  prepare  the  acid  salts,  it  is  simply  necessary  to  incom- 
pletely saturate  the  acid;  one-half  in  the  case  of  dibasic  acids, 
one- third  or  two- thirds  in  the  case  of  tribasic  acids,  etc. 

The  hydrogen  of  the  CH2  group  in  carboxyl-ketonic  acids 
is  replaced  by  a  metal  not  only  by  the  action  of  metallic  sodium, 
or  sodium  alcoholate,  but  even  by  double  decomposition  with 
salts.  The  copper  salt  of  acetyl-acetic  ester  separates  in  the 
form  of  a  precipitate  insoluble  in  water  when  a  solution  of  copper 
acetate  is  added  to  an  alcoholic  solution  of  aceto-acetic  ester. 
The  hydrogen  of  the  CH2  of  malonic  ester  behaves  in  the  same 
manner,  as  is  also  the  case  with  the  hydrogen  of  the  so-called 
nitro  compounds  of  the  aliphatic  series. 

The  hydrogen  of  the  NH  group  of  the  imides  may  also 
be  replaced  by  metals.  If  alcoholic  sodium  is  added  to  an 
alcoholic  solution  of  succinimide,  followed  by  the  addition 
of  ether,  there  is  precipitated  C^C^.NK  +  JH^O.  The  silver 
derivative,  C4H402.NAg,  is  formed  when  silver  nitrate  is  added 
to  an  alcoholic  solution  of  succinimide  containing  a  little 
ammonia. 

When  a  halogen  is  replaced  by  a  metal,  there  are  formed 
the  metallo-organic  compounds.  In  certain  cases  these  com- 
pounds are  the  result  of  a  reaction  between  the  intermediate 
products  at  first  formed.  As  the  metals  which  form  such 
compounds  are  generally  polyatomic,  there  is  a  condensation 
during  the  formation  of  the  organo-metallic  compounds,  and 
an  indirect  complication  of  the  molecule. 


CHAPTER  IV. 
REMOVAL  OF  RADICALS. 

General  Considerations.  —  The  removal  of  halogens  and  of 
the  elements  of  water  from  organic  compounds  may  take  place 
when  an  atom  of  carbon,  to  which  the  halogen  or  OH  is  attached, 
is  connected  with  one  or  more  other  atoms  of  carbon.  The 
hydrogen  which  is  removed  is  the  one  fixed  to  the  neighboring 
carbon  atom  having  the  least  number  of  hydrogen  atoms.1 
Thus: 

CH3.CC1  =  CH2    gives    CH3.C^CH. 

a-Chlor-propylene.  Allylene. 

CH3  CH3 

I  I 

CH.OH        gives    CH 

I  II 

CH(CH3)2  C(CH3)2 

Secondary  methyl-  Trimethyl- 

isopropyl-carbinol.  ethylene. 

If  there  is  no  hydrogen  fixed  to  the  neighboring  carbon 
atom  instead  of  a  removal  of  groups,  there  will  be  a  substitu- 
tion. Thus,  with  alcoholic  potash: 

CH2 


CH3.C.CH2C1    gives  CH3.C.CH2.O.C2H5. 

Iso-dimethyl-  Ethony  compound  of 

ethylene  chloride.  iso-dimethyl-ethylene. 

CHC13    gives  CH(O.C2H5)3. 

Chloroform.  Ortho-formic  ester. 


1  See  V.  Markovnikoff,  The  Reciprocal  Action  of  Atoms  on  One  Another  in  Chemi- 
cal Compounds,  Kasan,  1869  (in  Russian).  Also  A.  Zaytzeff,  On  the  Conditions 
of  Fixation  and  Removal  of  the  Elements  of  Hydriodic  Acid  in  Organic  Compound* 
(Jour.  Soc.  Phys.  Chim.  Russe,  vol.  17,  p.  289). 

108 


REMOVAL   OF  RADICALS  109 

The  alpha  isomers  of  the  halogen  substitution  derivatives 
of  the  acids  lose  their  halogen  with  difficulty.  With  alkalies 
they  exchange  the  halogen  for  hydroxyl.  Thus  a-chlor-pro- 
pionic  acid  is  converted  completely  into  lactic  acid,  but  the 
«-brom  acid  is  converted  partly  into  lactic  acid  and  partly 
into  acrylic  acid:  ^-chlor-  and  brom-propionic  acids  give 
only  acrylic  acid. 

Some  /?-brom  acids,  heated  for  a  long  time  with  water,  give 
the  unsaturated  acids  and  certain  decomposition  products. 
By  removing  the  halogens  from  gamma  derivatives,  inner 
anhydrides,  or  lactones,  are  formed.  In  the  aromatic  series 
the  beta  derivatives  behave  in  the  same  manner.  Cold  water 
is  sometimes  sufficient  to  bring  about  this  reaction.  When  the 
body  contains  two  halogen  atoms,  they  may  be  removed  simul- 
taneously, the  hydrogens  attached  to  the  most  hydrogenated 
carbon  atom  being  removed  at  the  same  time. 

RCH2.CC12.CH3  gives    R.CH2.C^CH. 

^,\CH.CC12.CH3         gives  ] 

^SCH.CH.CH.CHg  gives    } 

I      I 
Br  Br 

Removal  of  Hydrogen. — For  the  direct  removal  of  this 
element  see  that  of  Br. 

Removal  of  Oxygen. — (See  previous  pages.) 


A.  Removal  of  the  Halogens. 

The  removal  of  chlorine  may  be  brought  about  by  the 
action  of  nascent  hydrogen  (sodium  amalgam  and  water,  iron 
and  acetic  acid,  zinc  and  sulphuric  acid,  zinc  powder  or  cop- 
per and  water),  but  generally  it  is  necessary  to  heat  the  com- 


no  ORGANIC  SYNTHESES. 

pound  with  sodium.  Sometimes  the  removal  of  chlorine  is 
brought  about  by  simply  heating  the  body.  Thus,  by  passing 
the  vapor  of  hexachlor-ethane,  CC13.CC13,  through  a  heated 
tube,  ethylene  perchloride  is  obtained,  CC12  =  CC12.  There  is 
also  a  removal  of  chlorine,  at  times,  when  it  is  endeavored  to 
replace  this  halogen  with  iodine,  especially  if  the  atoms  of 
chlorine  are  not  fixed  to  a  single  carbon  atom. 

The  removal  of  bromine  is  carried  out  more  easily  than 
that  of  chlorine,  by  the  action  of  water,  of  sodium,  of  mer- 
cury, or  with  a  zinc-copper  element.  For  instance,  trimethylene 
may  be  prepared  by  heating  the  bromide  on  a  water-bath  with 
zinc  powder  and  dilute  alcohol.  In  the  same  manner  ethylene 
may  be  prepared  from  the  bromide,  C2H4Br2,  and  the  dibro- 
mide  of  acetylene,  C2H2Br2,  from  the  tetrabromide,  C2H2Br4.1 
Bromine  derivatives  treated  with  potassium  iodide  also  lose 
bromine : 

CH2.Br  .CHBr  .CO.OH + 2KI  =  CH2 :  CH.CO.OH  +  2KBr + 12. 

Dibrom-propionic  acid.  Acrylic  acid. 

In  the  same  manner,  fumaric  acid  may  be  prepared  from 
dibrom-succinic  acid: 


CH.Br.COOH  CH.COOH 

+  2KI=2BrK  +  I2  +  || 
.COOH  CH.COOH 


CH.Br.i 


In  order  to  neutralize  the  iodine  set  free  in  the  reaction,  metallic 
copper  is  added  to  the  mixture.2 

The  removal  of  iodine,  as  already  indicated  above,  takes 
place  sometimes  in  the  decomposition  of  the  iodine  compounds. 

B.  Removal  of  the  Halogen  Acids. 

The   removal  of    hydrochloric   acid    is   sometimes   brought 
about  by  heating.    Thus,  the  products  of  the  action  of  phos- 

1  See  A.  Sabaneff,  On  the  Compounds  of  Acetylene,  Moscow,  1881  (in  Russian). 

2  Berthelot's  method. 


REMOVAL  OF  RADICALS.  nr 

phorus  pentachloride  on  aldehydes,  ketones,  ketonic  acids,. 
amines,  anilides,  etc.,  often  lose  a  molecule  of  hydrochloric 
acid.  The  second  molecule  is  removed,  as  in  other  cases,. 
through  more  or  less  energetic  actions,  as,  for  example,  in  the 
preparation  of  ethylene  oxide  by  the  action  of  potash  on 
chlorhydrin  : 


C2H4.C1.0H  +  KOH  =  KC1  +  H20  + 


The  best  method  consists  in  using  an  alkaline  solution,  aqueous 
or  alcoholic,  and  hot  or  cold.1  Baryta-water  may  also  be 
used,  as  well  as  the  carbonate  of  silver  and  oxide  of  lead;  and 
even  recourse  may  be  had  to  distillation  with-  soda-lime.  With, 
aromatic  compounds,  the  removal  of  halogen  acids  only  takes 
place  in  cases  where  the  halogen  is  in  the  side-chain. 

The  removal  of  hydrobromic  acid  is  more  easily  brought 
about  than  that  of  hydrochloric  acid.  It  can  be  effected 
instantly,  as  when  the  unsaturated  acids  are  converted  into 
isomeric  lactones,  by  the  action  of  hydrobromic  acid.  Some 
methods  of  producing  the  unsaturated  compounds  are  based 
on  the  removal  of  hydrobromic  acid. 

The  removal  of  hydriodic  acid  is  very  easily  effected,  and 
very  frequently  the  iodine  compounds  are  used  for  the  prepa- 
ration of  unsaturated  derivatives.2  A  concentrated  alcoholic 
solution  of  potash  is  used.  This  acid  may  also  be  removed 
by  the  oxides  of  silver  or  lead,  and  even  with  acetate  of  lead, 
The  salts  of  hydriodic  acid  are  sometimes  decomposed  by 
heating  their  aqueous  solutions.  The  lead  salt  of  iodo-pro- 

1  With  an  alcoholic  alkaline  solution  there  is  usually  produced,  as  a  by-product, 
some  ethers  of  RC1,  as,  for  example,  R.OC2H5. 

2  Occasionally  through  the  removal  of  HI  there  are  obtained  two   isomeric 
hydrocarbons.     This  may,  perhaps,  be  attributed  to  the  action  of  the  alcoholic 
potash.     Compare    the   behavior  of    the  acetylene  hydrocarbons.     lodo-stearic 
acid  (action  of  HI  on  oleic  acid),  treated  with  alcoholic  potash,  loses  HI  and 
gives  ordinary  oleic  acid,  together  with  a  solid  isomer  of  the  latter. 


H2  ORGANIC  SYNTHESES. 


pionic    acid,    CH2LCH2.CO.OH,    gives    acrylic    acid;     in    a 
general  manner  this  reaction  may  be  written  as: 


C.  Removal  of  Water. 

In  di-  and  tri-hydrates,  in  f-hydroxy  acids,  and  some 
others,  the  removal  of  water  takes  place  at  the  moment  of 
their  formation.  But  generally  it  occurs  through  the  action 
of  heat  or  dehydrating  agents,  and  also  through  the  production 
of  intermediate  compounds.  Thus,  the  ethylene  hydrocar- 
bons are  obtained  by  the  distillation  of  the  corresponding 
alcohols  and  ethers. 

The  elements  of  water  may  be  removed  from  alcohols  by 
heating  them  with  fused  zinc  chloride,  or  by  gradually  adding 
them  to  phosphoric  anhydride.  The  latter  method  is  a  very 
convenient  one  for  the  preparation  of  the  gaseous  unsaturated 
hydrocarbons,  particularly  propylene.1  Water  may  also  be 
removed  from  alcohols  by  passing  their  vapor  over  heated 
zinc  powder.  Concentrated  (and  even,  in  some  cases,  dilute) 
sulphuric  acid  also  produces  the  same  result. 

At  the  same  time  that  the  desired  hydrocarbon  is  prepared, 
there  are  also  formed  its  isomers.  The  removal  of  water  is 
frequently  accompanied  by  reduction. 

The  /?-oxy  and  oxy-polycarboxylic  acids  behave  in  the 
same  manner  as  the  alcohols  with  regard  to  the  removal  of 
water  (distillation  of  the  free  acids,  action  of  dilute  sulphuric 
acid  and  heat,  phosphorus  chloride,  phosphoric  anhydride,  etc.)  : 
they  are  converted  into  the  unsaturated  acids.  Alexeyeff 
admits  the  following  series  of  transformations  :  2 

1  According  to  Beilstein. 

2  The  formation  of  pyruvic  acid  from  glyceric  acid  is  the  result  of  several 
successive  reactions.     It  is  very  probable  that  there  is  a  removal  of  /9-OH  and 
the  formation  of  an  unsaturated  oyx-  acid;   then,  by  the  fixation  and  subsequent 
loss  of  the  elements  of  water,  the  unsaturated  compound  is  converted  into  pyruvic 
acid. 


REMOVAL   Of  RADICALS.  "3 

€H2OH  CH2  CH3  CH3 

CH.OH    --  >    C.OH      --  >    C/^    --  >    CO 

I  I  I 

CO.OH  CO.OH  CO.OH  CO.OH 

Glyceric  acid.  Pyruvic  acid. 

It  is  to  be  remarked  that  the  transformation  of  pyruvic 
acid  from  glyceric  acid  is  analogous  to  the  production  of 
aldehyde  by  the  dehydration  of  glycol. 

The  ethers  of  the  a-acids,  in  which  OH  plays  the  role  of  a 
tertiary  alcohol,  are  likewise  comparable  to  the  alcohols. 
Thus,  methyl-acrylic  acid  is  obtained  by  the  action  of  phos- 
phorus trichloride  on  the  ether  of  a-oxy-isobutyric  acid: 


<rm 
CO 


CO  OH     -- 

CH3.C.CO.OH 

Generally,  the  a-oxycarboxylic  acids,  through  the  loss  of 
water  (by  the  action  of  heat),  give  anhydrides. 

The  dihydric  alcohols  are  also  converted  into  anhydrides 
(oxides)  by  the  removal  of  water.  This  reaction  is  easily  carried 
out  in  many  cases.  Thus,  by  boiling  with  dilute  sulphuric 
acid, 

C6H5CH.OH  C5H5.CH  v 

is  converted  into  ;>0. 

CH2.OH  CH/ 

Phenyl-glycol.  Phenyl-ethylene  oxide. 

The  removal  of  water  from  the  ordinary  glycols  of  the  ali- 
phatic series  (by  means  of  dehydrating  agents)  is  accompanied 
by  the  formation  of  isomerides.  The  compounds  formed  are 
not  true  anhydrides  but  isomers,  from  which  the  glycol  can- 
not be  again  regenerated  by  the  addition  of  water;  thus,  ordi- 
nary glycol  gives  ethyl  aldehyde: 

CH3 
CH2.OH  | 

I  --  >  c=o 

CH2.OH  | 

H 

Glycol.  Aldehyde. 


U4  ORGANIC  SYNTHESES. 

To  obtain  the  true  anhydrides  it  is  necessary  to  remove  the 
elements  of  hydrochloric  acid  from  the  mono-chlorhydrins : 

CH< 


VXl2.Vyl  V-LJ.2v 

|  -HC1=  |       >0 

CH2.OH  CH/ 

Chlorhydrin  of  glycol.          Ethylene  oxide. 


The  f-hydroxy  acids,  as  remarked  above,  lose  water  when 
they  are  formed;  on  this  account  the  lactones  are  always 
formed  in  their  place.  Thus,  by  the  oxidation  of  isocaproic. 
acid, 

(CH3)2.CH 

CH2 

there  is  obtained 
CH2 


C0.< 


.OH  CO- 

Iso-caproic  acid.  Caprolactone. 

In  the  same  manner,  by  the  reduction  of  levulinic  acid 
(a  f-ke tonic  acid),  in  place  of  obtaining  the  corresponding 
hydroxy  acid,  there  is  formed  valero-lactone : 

CH3.CO 
CH 
CH2 
CO.OH  CO 

Levulinic  acid.  Valero-lactone. 

The  removal  of  water  from  the  aromatic  hydroxy  acids 
(OH  fixed  to  the  benzene  nucleus)  takes  place  rather  diffi- 
cultly; it  is  necessary  to  subject  the  body  to  dry  distillation, 
or  to  the  action  of  'concentrated  hydrobromic  acid.  In  this 
manner  it  is  possiole  to  obtain  coumarin  from  coumaric  acid. 

The  dicarboxylic  acids  behave  in  the  same  manner  as  the 


REMOVAL   OF  RADICALS.  115 

•a-hydroxy-acids;  by  heating  them,  or  by  the  action  of  dehy- 
drating agents,  they  are  converted  into  anhydrides.  The  acids 
of  the  aliphatic  series,  which  have  two  carboxyl  groups,  united 
the  one  to  the  other  (as  in  oxalic  acid),  or  with  one  or  two 
.atoms  of  carbon  (malonic  acid  and  its  homologues),  do  not 
give  anhydrides,  but  are  decomposed,  giving  rise  to  carbonic 
acid  and  a  mono-basic  acid: 


+  CH3.CO.OH. 


Malonic  acid.  Acetic  acid. 

In  the  aromatic  series,  the  anhydrides  are  formed  when 
the  two  carboxyl  groups  are  in  the  ortho  position  with  refer- 
ence to  one  another,  or  with  reference  to  the  point  which  unites 
two  benzene  residues. 

Simultaneously  with  the  anhydride,  there  are  formed,  in 
certain  cases,  ketonic  acids.  Diphenic  acid,  moderately  heated 
with  concentrated  sulphuric  acid,  gives  diphenyl-ke  tonic  acid: 

C6H4.CO.OH  C6H4X 

I  -*    I     >o 

C6H4.CO.OH  C6H3< 

XXXOH. 

Some  dicarboxylic  acids  are  convered  into  anhydrides  by 
a  prolonged  fusion,  others  by  repeated  distillations,  and 
some  by  acetic  anhydride  or  acetyl  chloride.  To  remove 
the  water,  sulphuric  acid  may  be  used,  and  also  the  chlo- 
rides and  oxy  chlorides  of  phosphorus.  When  acetyl  chloride 
is  employed,  it  is  necessary  to  remember  that  the  hydroxy- 
dicarboxylic  >  acids  give  acetyl  anhydrides,  and  the  unsatu- 
rated  di-acids  are  converted  into  chlorine  derivatives  of  the 
desired  acid. 

The  ammoniacal  salts  of  the  acids,  when  heated,  lose  water 
and  form  the  amides  of  the  corresponding  acids: 

R.CO.ONH4  -  H20  -  R.CO.NH2. 


Il6  ORGANIC  SYNTHESES. 

Dry  distillation  is  sufficient,  but  in  the  majority  of  cases 
the  salt  is  dissociated,  and  is  decomposed  into  the  acid  and 
ammonia.  This  is  particularly  so  with  ammonium  acetate 
CHs.CO.ONELt,  when  there  is  only  a  yield  of  25  per  cent.;  by 
distilling  sodium  acetate  with  ammonium  chloride,  the  same 
result  is  obtained.  Better  results  are  obtained  if  the  salt  is 
heated  in  an  autoclave  for  five  or  six  hours  at  220°  C,  when 
the  yield  is  80  to  85  per  cent,  of  the  theoretical.  Some  aro- 
matic acids  give  a  slightly  better  yield  than  this.1 

In  some  cases  (for  example,  in  heating  the  ammonium  salt 
of  isobutyric  acid)  a  secondary  amide  is  formed  simultaneously 
with  the  primary  amide. 

The  dicarboxylic  acids,  on  heating,  behave  in  the  same 
manner:  with  the  acid  salts  there  are  formed  acid  amides;  with. 
the  neutral  salts,  amides. 

The  amido  acids,  on  losing  water,  are  converted  into  imides* 
This  reaction  sometimes  takes  place  in  attempting  to  form 
the  acid  amides.  Thus,  brom-succinic  ester,  heated  with  an. 
alcoholic  solution  of  ammonia,  gives  the  imide  of  aspartic  acid, 
instead  of  asparagine: 


C2H3Br(CO.OH)2        ->    C2 

Brom-succinic  acid.  Asparagine. 

and 


Imido-aspartic  acid. 

By  the  oxidation  of  ortho-sulpho-amidotoluene  there  is 
produced  simultaneously  amido-sulphobenzoic  acid  and  the 
imide  derivative,  saccharin,  a  substance  which  has  an  exceed- 
ingly sweet  taste: 

P  „  /CH3  p  „  /CO.OH       p  „  /CO  \NH 

C6H4\S02.NH2    C6H4\S02.NH?    CfiH4\S02/NH2- 

Ortho-sulpho-amidotoluene.  Amido-sulphobenzoic  acid.  Saccharin. 

1  With  respect  to  the  time  and  temperature  of  the  reaction  for  different  acids, 
see  Menchoutkine,  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  16,  p.  191,  and  vol.  17,. 
p.  259. 


REMOVAL  OF  RADICALS.  1 i 7 

The  amides,  by  the  loss  of  water,  are  changed  into  nitriles: 


C6H5.CO.NH2    gives    C6H5.C^N. 

Benzamide.  Benzo  nitrile. 


It  rarely  happens  that  water  may  be  removed  from  amides- 
by  simply  heating,  but  the  intervention  of  a  dehydrating  agent 
is  required  (such  as  P205,  PC15,  P2S5,  and  ZnCl2). 

In  order  to  obtain  nitriles,  one  may  start  with  the  ammo- 
nium salt  of  the  corresponding  acid  and  treat  it  with  phos- 
phoric anhydride.  The  aromatic  nitriles  are  also  obtained  by 
the  action  of  lead  sulphocyanide  on  the  acids: 


2C6H5.CO.OH  +  Pb(CNS)2  =  2C6H5CN  +  PbS  +  H2S  +  2C02. 

Benzoic  acid.  Benzonitrile. 


The  ortho-amido-anilides  (1.2),  on  losing  water,  give  sub- 
stituted derivatives  of  the  amidines: 


p   TT          (I)    NH2  TJ   n       p   TT  /N      \p 

CeH4(2)  NH.CO.CH3~M2°  =  UH4C. 


The  removal  of  water  takes  place  at  the  moment  of  for- 
mation of  ortho-amido-anilide  (by  the  action  of  the  chloride 
of  the  acid,  or  of  the  acid  itself,  on  the  ortho-diamido  com- 
pound). Some  apparent  anhydrides  are  obtained  with  the 

derivatives  of  ortho-amido-phenol.    Thus,  CeH^  ~  ^C.CeHs  is- 

prepared  by  the  reduction  of  C6H4<^  Q  QQ  n  jj  >  or  is  produced 

in  the  action  of  benzoyl  chloride  on  ortho-amido-phenol. 

The  aldoximes  R.CH:N.OH,  by  the  loss  of  water  (with 
acetic  anhydride),  are  converted  into  nitriles,  RC:N. 

Some  compounds  containing  nitrogen  are  easily  decom- 
posed with  loss  of  water.  The  oxidation  of  choline, 


Ii8  ORGANIC  SYNTHESES. 

CH2.OH  CO.OH 

,  instead  of  giving  |  ,  furnishes 

CH2.N(CH3)3OH  CH2N(CH3)3OH 

CO-0 
the  anhydride  of  betaine,  |       | 

CH2N(CH3)3 

The  diazo  bodies  of  the  phenols  and  the  sulphonic  acids 
lose  water  at  the  moment  of  their  formation.  For  example, 
with  the  amido-sulphonic  acid, 

p  TT  /S02.OH 
UH4\NH2      ' 

in  place  of  obtaining 

wehave    C6 


Nitro-amidobenzoic   acid,   C6H3(NH2)(N02)CO.OH,  in  the 
same  manner,  with  nitrous  acid,  gives: 


The  nitrites  of  the  secondary  amines  and  of  the  esters 
of  "the  amido  acids  of  the  fatty  series  are  very  unstable  com- 
pounds which  decompose  with  loss  of  water,  and  the  forma- 
tion of  nitroso-amines  and  esters  of  the  diazo-acids.  Thus: 

C8H!  7N.HN02  -  H20  =  C8H16(NO)N. 

Nitroso-conine. 


CH2.NH2.HN02  CH<  || 

|  -2H20=  |     XN 

C02.C2Hs  C02.C2H5. 

Nitrite  of  glycocoll  ester.  Diazo-acetic  ester. 

The  nitrite  of  glycocoll  may  be  obtained  by  double  decom- 
position between  the  hydrochloride  of  the  ester  of  glycocoll 


REMOVAL   OF  RADICALS.  119 

(action  of  HC1  in  absolute  alcohol  on  the  acid  amide)  with  sil- 
ver nitrite.  The  ester  of  the  diazo-acid  is  obtained  by  adding 
potassium  nitrite  to  a  solution  of  the  hydrochloride  of  the 
ester  of  glycocoll;  by  the  action  of  hydrochloric  acid,  there  is 
a  splitting-off  of  water  and  the  formation  of  the  diazo-com- 
pound. 

With  the  nitrite  of  aspartic  ester  there  is  obtained  the 
ester  of  diazo-succinic  acid: 


C(N  =  N)CO.OH 
.OH 


CHo.CO.< 


The  diazo-acids  of  the  aliphatic  series  are  stable  only  in 
the  form  of  esters  or  amides;  when  liberated  they  decom- 
pose with  loss  of  nitrogen.  By  the  removal  of  water  from 
the  ammonium  compounds  of  the  aldehydes,  there  may  be 
obtained  artificially  the  homologues  and  analogues  of  pyridine. 
Acrolein-ammonia  on  distillation  gives  picoline  (/?-methyl- 
pyridine);  with  the  ammonia  derivative  of  crotonic  aldehyde, 
collidine  (methyl-ethyl-pyridine)  is  produced.  The  alkamine, 

(CH3)2.C— CH2 
NH/       \CH.OH, 

(CH3)2.C-CH2, 

which  is  obtained  by  the  reduction  of  triacetonamine,  gives, 
with  sulphuric  acid,  the  poisonous  alkaloid  triacetonine : 

(CH3)2.C— CH 

NH/       NcH. 
(CH3)2.C— CH2 

By  heating  normal  butyric  acid  with  pentasulphide  of 
phosphorus,  using  two  to  three  times  the  theoretical  quantity, 
there  is  formed  thiophene,  C4H4S.  Its  formation  can  be  regarded 


120  ORGANIC  SYNTHESES. 

as  a  removal  of  water  and  hydrogen  from  the  thio-butyric  acid, 
CH3.CH2.CH2.CO.SH,  which  is  at  first  formed. 

D.  Removal  of  Ammonia,  NH3. 

When  the  diamines  and  the  diamides  are  heated  they 
lose  NH3  and  form  imines  and  imides.  Thus  succinamide 
gives  succinimide: 


CH2.CO.NH2  CH2.C(X 

-NH3  =  |  >NH. 

[2.CO.NH2  CH2.CO 


-•"•-. 
CH. 


The  hydrochloride  of  ethylene-diamine  is  decomposed, 
when  heated,  into  ammonium  chloride  and  the  hydrochloride 
of  the  imine: 

CH2.NH2.HC1  CH2X 

|  =NH4C1+  |        >NH.HC1. 

CH2.NH2.HC1  CH/ 

By  even  distilling  the  hydrochloride  of  pentamethylene- 
diamine  (reduction  of  the  cyanide  of  trimethylene)  there  is 
formed,  at  the  same  time  with  ammonium  chloride,  some  of  the 
hydrochloride  of  piperidine: 

nTT   /CH2.CH2.NH2.HC1       ATTT  pi    ,   PTT  / CH2.CH2\ATTT  Tr™ 

CH2\CH2.CH2.NH2.HC1 =NH4C1  +CH2\CH2.CH2/NH-HCL 

E.  Removal  of  Hydrogen  Sulphide. 

The  substituted  thio-ureas  lose  hydrogen  sulphide  when 
treated  with  lead  oxide,  or  with  freshly  precipitated  mercury 
oxide.  Thus: 

n.    r/NH.CH3 

—  X12O=^X  XT 


-2 
Methyl-thio-urea. 

'NH.C6H5 
>TH.C6H5 

Diphenyl-thio-urea. 


REMOVAL   OF  RADICALS.  121 

The  same  thio-ureas  of  the  aliphatic  series  may  be  obtained 
by  heating  the  salts  of  the  thio-carbamic  acids  (obtained  by 
the  union  of  CS2  with  RNH2)  with  alcohol  in  sealed  tubes  to 
110-120°  C.,  thus  causing  a  removal  of  hydrogen  sulphide: 

KH.C2Hs      _TT  Q_ap/NH.C2H5 
S.NH3.C2H5  ^XNH.CaHs' 

The  product  obtained  by  the  combination  of  diethyl- 
amine  with  carbon  disulphide, 

™/N(C2H5)2 
U\S.NH2(C2H5)2> 

is  a  stable  enough  compound  in  the  sense  that  it  does  not 
lose  hydrogen  sulphide  even  when  treated  with  metallic  oxides, 
but  it  is  decomposed  into  diethyl-amine  and  a  salt  of  diethyl- 
thio-carbamic  acid. 

The  substituted  dithio-carbamic  acids  are  converted  into 
isosulphocyanic  esters  by  loss  of  hydrogen  sulphide : 


.R 

SH 


As  the  acids  themselves  are  not  very  stable,  their  lead 
or  silver  salts  are  used. 

In  order  to  prepare  the  isosulphocyanates  of  the  aliphatic 
series,  it  is  not  necessary  to  isolate  the  salts  of  the  dithio-car- 
bamic acids;  the  mixture  obtained  by  the  union  of  the  amine 
with  carbon  disulphide  and  the  theoretical  quantity  of  mer- 
curic chloride  may  be  distilled  directly.  The  product  of  the 
union  of  2R.NH2  with  carbon  disulphide  may  also  be  treated 
with  an  alcoholic  solution  of  iodine. 

F.  Removal  of  Sulphuric  Anhydride  (S03). 

The  removal  of  S03  takes  place  by  heating  the  sulphonic 
acids  with  water;  with  hydrochloric  and  hydrobromic  acids 
to  150-250°,  and  by  the  dry  distillation  of  the  sulphonic 


122  ORGANIC  SYNTHESES. 

acids.  This  reaction  is  very  often  employed  for  the  purifi- 
cation and  separation  of  the  hydrocarbons,  CnH2n-6;  the  best 
means  of  conducting  this  decomposition  is  with  superheated 
steam.  The  dry  salt  of  the  sulphonic  acid  is  mixed  with 
3  parts  of  sulphuric  acid  and  1  part  of  water  and  heated  to 
180-220°  C.;  there  is  then  passed  a  current  of  superheated 
steam  through  the  mixture. 


G.  Removal  of  Carbon  (C). 

This  is  a  very  rare  reaction;  the  only  example,  perhaps, 
is  the  formation  of  protocatechuic  aldehyde,  C7H603,  from 
piperonal,  C8H603,  by  heating  this  body  in  a  sealed  tube  with 
hydrochloric  acid: 

/CHO  /CHO 


C6H3(-0\rn  =C6 

\0/C  \OH 

Piperonal.  Protocatechuic 

aldehyde. 

Another  example  of  this  removal  would  be  nitrophthalide, 
C8H5N04,  that  Dussar  is  said  to  have  obtained  by  the  action 
of  potash  and  calcium  hydrate  on  nitronaphthalene,  Ci0H7N02; 
but  in  reality  there  may  be  only  a  removal  of  the  impurities 
in  the  nitronaphthalene,  and  it  is  doubtful  if  nitrophthalide 
is  formed.1 

H.  Removal  of  Carbon  Monoxide  (CO). 

The  aldehydes  and  ketones,  on  energetic  heating,  lose  CO. 
Thus  benzoic  aldehyde,  C6H5.CHO,  gives  benzene,  C6H6;  benzo- 
phenone,  C6H5.CO.C6H5,  and  acetophenone,  C6H5CO.CH3, 
are  transformed,  the  first  into  diphenyl,  C6H5.C6H5,  the  second 
into  toluene,  CeH5.CH3.  This  reaction  is  not  very  complete 
as  there  is  formed  a  large  amount  of  other  products. 

1  See  Fehling's  Handworterbuch,  Bd.  V,  p.   508,  and  Jour.  Soc.  Phys.  Chim. 
Russe,  vol.  2,  p.  266.     See  also  Annalen,  vol.  202,  p.  219. 


REMOVAL   OF  RADICALS.  123 

I.  Removal  of  Carbonic  Acid  (C02). 

The  monocarboxylic  acids  of  the  formula  R.COOH,  by  losing 
C02,  give  the  hydrocarbons,  RH;  it  is  only  necessary  to  heat 
them  with  the  hydrates  or  oxides  of  calcium  or  barium. 

The  dicarboxylic  acids  of  the  aliphatic  series  lose  C02  much 
more  easily,  and  are  converted  into  a  monocarboxylic  acid  when 
the  two  COOH  groups  are  attached  to  a  single  carbon  atom. 
Such  are  malonic  acid  and  its  substituted  derivatives.  Thus, 
methyl-malonic  acid  (iso-succinic)  is  split  up  into  carbonic 
and  propionic  acids: 

CH3 

<r   nr^r^TT  =C02+ 

COOH 


CH2 


It  is  only  necessary  to  fuse  the  acid  and  heat  it  to  180- 
220°  C. 

Some  tricarboxylic  acids  are  also  decomposed  easily;  for 
example,  aconitic  acid.  Desoxalic  acid  heated  in  aqueous  solu- 
tion is  decomposed  into  C02  and  para-tartaric  acid. 

Acids  which  yield  anhydrides  (oxalic,  succinic)  lose  C02 
under  the  influence  of  uranium  salts  (particularly  the  nitrate) 
when  exposed  to  sunlight.  To  remove  C02  from  aromatic 
dibasic  acids,  they  are  heated  with  lime. 

It  is  possible  to  remove  more  than  one  C02  group  from 
polycarboxylic  acids.  Thus  mellitic  acid,  on  dry  distillation, 
gives  pyromellitic  acid, 

C6(COOH)6-2C02  =  C6H2(COOH)4; 

and,  by  heating  with  soda-lime,  benzene  is  produced: 
C6(COOH)6-6C02  =  C6H6. 

Mellitic  acid  above  200°  C.  loses  2C02;  fused  with  soda, 
it  gives  benzene  and  carbonic  acid. 


124  ORGANIC  SYNTHESES. 

To  remove  C02  from  chlorinated  products  of  the  aromatic 
acids  they  are  heated  in  a  sealed  tube  with  dilute  sulphuric 
acid;  distillation  with  lime  would  remove  the  halogen. 

The  nitro-carboxylic  acids  lose  C02  less  easily.  However, 
the  alkaline  dinitro-phenyl-acetates  are  decomposed  slowly 
at  the  ordinary  temperature,  and  instantly  on  boiling  with 
water: 

XI)  N02  XI)  N02 

C6H3A3)  N02  +  H20  =  C6H3A3)  N02+C03HK. 

\(4)  CH2COOK  \(4)  CH3 

Dinitro-phenyl-acetate  Dinitro-toluene. 

of  potassium. 

The  amino-acids  are  easily  converted  into  amines  by  heat- 
ing alone,  or  with  soda-lime;  with  caustic  potash  or  with 
baryta- water  in  sealed  tubes.  Glycocoll  gives  methylamine, 
and  the  amino-benzoic  acids  give  aniline. 

The  aliphatic  hydro xy-acids  lose  C02  with  difficulty;  for 
if  they  are  heated,  in  the  majority  of  cases,  they  are  decom- 
posed, with  loss  of  water  or  formic  acid.  Sometimes  the  removal 
of  C02  is  accompanied  by  the  loss  of  water.  This  occurs,  for 
instance,  in  the  preparation  of  pyruvic  acid,  starting  from  tar- 
taric  acid,  although,  in  fact,  this  reaction  may  be  more  com- 
plicated, the  formation  of  pyruvic  acid  taking  place  through 
the  intervention  of  unsaturated  compounds: 

CH(OH)CO.OH    CH2  CH3  CH3 

I  -II  H  -I 

CH(OH)CO.OH    C(OH)CO.OH    C(OH)2CO.OH    CO:CO.OH 

Tartaric  acid.         Removal  of  CO2  +  H2O.      Fixation  of  H2O.         Pyruvic  acid. 

It  may  be  admitted  that  tartaric  acid  at  first  loses  CO2 
and  gives  gly eerie  acid,  which  then  will  give  pyruvic  acid. 

Tartronic  acid,  by  the  loss  of  water,  gives  glycoUic  acid  (in 
fact,  its  anhydride) : 

CH2.OH 

co.OH— co2=| 

COOH. 
CO.OH 


REMOVAL  OF  RADICALS.  125 

The  aromatic  hydro xyl  acids  readily  lose  CO  2  on  distillation, 
alone  or  mixed  with  pumice-stone,  lime,  or  baryta.  Gallic 
acid  heated  with  water  in  a  closed  vessel  to  200-210°  C.  gives 
pyrogallol  through  loss  of  C02;  with  phloroglucic  acid, 
C6H2(OH)3COOH,  the  decomposition  takes  place  more  read- 
ily, the  latter  being  converted  completely  into  phloroglucinol 
by  simply  boiling  with  water. 

Pyridine-  and  quinoline-carboxylic  acids,  on  distillation  with 
lime,  are  decomposed  with  loss  of  C02.  Thus,  nicotinic  acid 
(/?-pyridine-carboxylic  acid)  gives  pyridine.  The  pyridine- 
dicarboxylic  acids,  when  heated  alone,  give  pyridine-carboxylic 
acids;  the  a-/?-dicarboxylic  acid  gives  nicotinic  acid: 

C5H3(COOH)2N  -C02  =  C5H4(COOH)N. 

If  it  is  distilled  with  lime,  two  C02  groups  are  removed. 

Ketonic  acids,  such  as  aceto-acetic  acid  and  others  in  which 
the  CO  and  COOH  groups  attached  to  one  and  the  same  carbon 
atom,  lose  C02  with  especial  ease  (some  above  100°  C.),  and  are 
converted  into  ketones : 

C6H5.CO.CH2.COOH-C02  =  C6H5.CO.CH3. 

Sometimes  the  splitting  off  of  C02  takes  place  at  the  moment 
of  formation  of  a  compound.  Thus,  in  treating  an  aqueous  solu- 
tion of  the  salt  of  iso-dibrom-succinic  acid  with  silver  oxide, 

CBr2.COOH  CO.COOH 

|  in  place  of  obtaining    | 

CH2.COOH  CH2.COOH 

there  is  obtained  the  decomposition  product,  pyruvic  acid  and 
C02: 

CO.COOH  CO.COOH 

I  -C02=| 

CH2.COOH  CH3 


126  ORGANIC  SYNTHESES. 

In  order  to  obtain  ketones  from  the  ketonic  acids,  they 
are  decomposed  with  a  dilute  solution  of  caustic  potash. 

In  certain  cases  it  is  preferable  to  heat  the  ester  with  dilute 
sulphuric  and  hydrochloric  acids,  or  with  water  alone.  The 
esters  of  the  diketonic  acids  may  be  used  in  the  same  manner 
(the  dike  tones  are  easily  decomposed  with  alkalies),  as  well  as 
the  halogen  substitution  products  of  the  ketonic  acids. 

There  are  some  ketonic  acids  containing  CO  and  COOH 
groups  attached  to  a  single  carbon  atom,  which  are,  however, 
more  stable;  these  are  not  decomposed  by  saponification  of  their 
esters;  they  lose  C02  only  after  energetic  heating;  for  example, 
the  body 

TJ  r\  r*(~\  C*  TT 

-Ll2V->\  /\J\J.\JQLi5 

l>< 

H2(X       XJO.OH 
\ 

Pyruvic  acid,  heated  with  dilute  sulphuric  acid,  loses  C02 
and  gives  the  aldehyde : 

CH3.CO.CO.OH  -  C02  -  CH3.COH. 


Phenyl-glycidic  acid,      C9H803  =          CH' 

CO.OH 

at   the   ordinary  temperature,  is   decomposed  with  liberation 
of  C02. 

J.  Removal  of  Formic  Acid  (HCO.OH). 

Hydrophthalic  acid,  C8H804,  with  sulphuric  acid,  gives 
phthalic  acid,  at  the  same  time  with  benzoic  acid,  carbon 
monoxide,  and  water : 

C8H804  =  C7H602  +  CO  +  H20. 


REMOVAL  OF  RADICALS.  127 

K.  Removal  of  Acetic  Acid  (CH3.CO.OH). 

(See  Chapters  VII  and  VIII.) 

L.  Removal  of  a  Hydrocarbon. 

This  reaction  occurs  in  the  decomposition  of  the  esters  of 
the  alcohols.  The  action  of  phosphoric  anhydride  on  phenols 
also  takes  place  in  the  same  manner.  Thymol,  for  example, 
is  decomposed  into  propylene  and  meta-cresol : 

C6H3^(3)  OH3  - 
\4)  C3H5 

M.  Removal  of  Alcohol  (R.OH). 

In  a  body  which  readily  loses  water,  if  the  hydrogen  of  the 
OH  group  is  replaced  by  a  radical  R,  for  example,  C2H5,  it  is 
almost  certain  that  the  compound  will  be  decomposed  with  loss 
of  alcohol.  The  hydrates  of  substituted  ammonias  behave  in 
the  same  manner;  on  heating  them,  they  are  decomposed  into 
a  compound  in  which  the  nitrogen  is  triatomic,  and  into  an 
alcohol,  or  the  products  of  its  decomposition,  hydrocarbon  and 
water. 

N.  Removal  of  Simple  Ethers. 

The  halogen  products  of  the  ammonium  compounds,  like 
RiNI,  are  decomposed  by  strong  heat  into  NR3  and  IR.  If 
the  four  radicals  are  not  identical,  and  if  they  include  a  CH3 
group,  the  latter  will  combine  with  the  halogen. 

O.  Removal  of  Amines  (NH2R). 

The  symmetrical  urea  compounds  are  decomposed  by  the 
action  of  acids  into  isocyanic  esters  and  amines  : 

'          =  CO.N.C2H5 + NH2.C2H5. 


128  ORGANIC  SYNTHESES. 

The  thio-ureas  behave  in  the  same  manner,  and  this  reac- 
tion is  utilized  for  the  preparation  of  iso-sulphocyanides  of  the 
aromatic  series;  the  reaction  also  takes  place  in  the  aliphatic 
series,  but  it  is  not  made  use  of. 

In  the  aromatic  series,  the  thio-ureas  are  heated  with  sul- 
phuric or  hydrochloric  acid;  it  is  better,  however,  to  use  a  con- 
centrated solution  of  phosphoric  acid  (sp.  gr.  =  1.7),  two  or 
three  parts  of  this  solution  to  one  part  of  the  thio-urea.  After 
heating  for  a  short  time,  the  iso-sulphocyanate  is  volatilized 
with  steam,  and  in  the  residue  the  amine  is  removed  with  an 
alkali.  Diphenyl-thio-urea  is  thus  completely  deomposed  : 


When  the  thio-ureas  contain  two  different  radicals,  there 
are  obtained  two  sulphocyanides  and  two  amines,  the  decom- 
position being  effected  in  two  directions  : 


CS/NjHp 
^\|NHR'| 


CHAPTER  V. 
DIRECT  FIXATION  OF  GROUPS. 

I.  GENERAL  CONSIDERATIONS. 

IN  the  direct  fixation  of  halogen  acids l  to  unsaturated 
hydrocarbons,  the  halogen  attaches  itself  to  the  carbon  atom 
having  the  least  amount  of  hydrogen.2  In  cases  where  two 
atoms  of  carbon  may  be  equal  in  this  respect,  the  halogen 
combines  with  that  one  to  which  a  methyl  group  (CH3)  is 
attached : 

(CH3)2C  =  CH2     with  HC1  ->    (CH3)2CC1.CH3. 


1  See   Markovnikoff   and  A.  Zaytzeff    as   referred    to  on   p.   108.     See    also 
Kablukoff,  On  the   Triatomic  Alcohols  and  their  Derivatives,  Moscow,   1887  (in 
Russian). 

2  Among  the  unsaturated  hydrocarbons,  those  containing  a  carbon  atom  at- 
tached to  the  least  number  of  hydrogen  atoms  combine  the  most  readily  with 
the  halogen  acids.     This  property  may  be  used  for  the  separation  of  isomers. 
Thus,  the  two  isomeric  amylenes 

(CH3)2.CH.CH=CH8 

Iso-propyl-ethylene 
and 


Methyl'-ethyl-ethylene 

•cannot  be  satisfactorily  separated  by  distillation,  as  the  former  boils  at  21°  C. 
and  the  latter  at  32°  C.  At  20°  C.,  however,  the  latter  alone  gives  the  iodo-com- 
pound: 


and  this  boils  at  above  100°  C. 

129 


130  ORGANIC  SYNTHESES. 

With  hydrocarbons  having  the  group  —  C=C  —  ,  two  atoms 
of  the  halogen  are  fixed  to  the  carbon  atom  with  the  least 
hydrogen. 

CH3.C^CH    withHCl-*    CH3.CG12.CH3. 

Aldehydes  and  unsaturated  acids,  by  the  fixation  of  a  halo- 
gen acid,  most  often  form  the  /^-substituted  body  of  the  saturated 
compound  : 

CH2  :  CH.CO.OH  +  HC1  =  CH2.C1.CH2  CO.OH. 

Acrylic  acid.  ^-chlor-propionic  acid. 

CH2  :  CC1.CO.OH  +  HC1  =  CH2C1.CHC1.CO.OH. 

C\ 
With     oxides    containing    the  |  />O   group,    the    halogen 


attaches  itself  to  the  carbon  atom  with  the  most  hydrogen, 
and  the  OH  group,  which  is  formed,  to  the  carbon  atom  with 
the  least  hydrogen: 


CH 
HO.OC.CH 


2\0  +  HC1  =  CH2.C1.CH(OH)  .CO.OH. 


It  is  possible  to  obtain  in  this  manner  the  iodo  substitution 
products  of  the  alcohols: 


0  +  HI=CH3.CH(OH).CH2L 


In  the  fixation  of  the  halogen  acids  to  the  unsaturated  alco- 
hols, there  is  a  displacement  of  OH  by  halogen  (see  page  79). 

With  hydrobromic  acid,  there  are  often  two  isomers  formed; 
by  modifying  the  conditions  it  is  possible  to  direct  at  will  the 
reaction  in  one  way  or  the  other.  In  the  majority  of  cases  the 
reaction  proceeds  normally  (the  bromine  being  fixed  by  the 
carbon  atom  with  the  least  hydrogen)  if  the  hydrobromic  acid  is 
not  very  concentrated.  Thus,  brom-ethylene,  with  acid  satu- 


DIRECT  FIXATION  OF  GROUPS.  131 

rated  at  6°  C.,  gives  mostly  ethylene  bromide,  CH2Br.CH2Br; 
but  if  the  acid  is  diluted  with  two  volumes  of  water,  ethylidene 
bromide  is  formed,  CH3.CH.Br2.  The  temperature  of  the  reac- 
tion also  exerts  an  influence:  thus,  atropic  acid  (a-phenyl- 
acrylic),  CH2  =  C(C6H5).CO.OH,  at  100°  C.,  with  concentrated 
hydrobromic  acid,  gives  /?-brom-hydratropic  acid;  but  at  the 
ordinary  temperature,  a  mixture  of  the  a-  and  /9-acids  is  ob- 
tained. 

The  carbon  atom  to  which  the  halogen  attaches  itself,  in  the 
case  of  the  fixation  of  a  halogen  acid,  is  the  same  one  as  that 
to  which  the  OH  group  attaches  itself  in  the  case  of  the  fixation 
of  water. 

II.  FIXATION  OF  HYDROGEN  (H). 

(See  under  Chapter  II.) 

III.  FIXATION  OF  OXYGEN  (0). 

To  the  reactions  already  mentioned  in  Chapter  I,  there 
will  be  added  here  the  case  of  the  fixation  of  oxygen  to  com- 
pounds containing  sulphur,  nitrogen,  or  metals. 

The  sodium  mercaptan,  C2H5.SNa,  with  dry  oxygen,  com- 
bines with  02  and  is  converted  into  C2H5.S02Na.  The  same 
mercaptan,  as  well  as  other  bodies  of  the  type  R.SH,  are  oxi- 
dized by  nitric  acid,  and  by  the  fixation  of  03  give  the  acids 
R.S0.2OH.  The  .sulphur  compounds  R2S  are  oxidized  equally 
by  nitric  acid  or  potassium  permanganate;  by  regulating  the 
concentration  and  temperature,  it  is  possible  to  fix  0  or  02  and 
to  obtain  the  oxides  SOR2  or  the  sulphones  SO 2R2.* 

Iso-propyl-pseudonitrol,  (CH3)2C(NO)N02  (see  page  83),  oxi- 
dized with  chromic  acid,  is  converted  into  dinitro-isopropane, 
(CH3)2.C(N02)2  (?);  but  it  is  not  possible  to  affirm  that  there 
is  here  a  conversion  of  the  NO  group  into  N02.  It  may  be  that 
there  are  several  successive  reactions,  as,  for  example,  in  the 

1  See  A.  Zaytzeff,  Action  of  Nitric  Acid  on  some  Organic  Compounds  contain- 
ing Sulphur,  Kasan,  1868  (in  Russian). 


I32  ORGANIC  SYNTHESES. 

transformation  of  quinone-oxime  (nitrosophenol,  see  page  83) 
into  nitrophenol: 

/N.OH    OH  /N/OH 

C6H4<  |         +^H=C6H4<  N\OH 
M}  \OH 

Quinone-oxime.  Nitrophenol. 

Many  metallo-organic  compounds  readily  combine  with 
oxygen  and  form  oxides : 

(C2H5)3Sn  (C2H5)3Snv 

+  0=  >0. 

(C2H5)3Sn  (C2H5)3Sn/ 

When  zinc-ethyl  is  slowly  oxidized  in  ethereal  solution,  there 
is  formed  Zn  (C2H5)20,  and  finally  zinc  ethylate  (C2H50)2  Zn. 

IV.  FIXATION  OF  HALOGENS. 
A.  The  Fixation  of  Chlorine  (Cl). 

This  takes  place  directly  with  unsaturated  compounds,  such 
as  ethylene.  Chlorine  or  the  trichloride  of  antimony  is  used,  or 
the  body  is  slightly  heated  with  a  mixture  liberating  chlorine 
(Mn02  with  NaCl  and  H2S04).  Sometimes  with  chlorine  there 
are  formed  substitution  products;  this  reaction  is  indicated  by 
the  evolution  of  hydrochloric  acid  gas. 

It  is  necessary  to  take  into  account  the  part  played  by 
light  in  the  action  of  chlorine.  Thus,  a-propylene  chloride, 
CH3.CC1  =  CH2,  in  the  dark  gives  substitution  products;  in 
the  light,  an  addition  product.  The  unsaturated  compounds, 
when  brominated  or  iodinated,  likewise  fix  chlorine,  the  latter 
with  replacement  of  iodine  by  chlorine.  For  example,  allyl 
iodide,  CH2  =  CH.CH2I,  with  chlorine,  gives  the  trichlorhydrin 
of  glycerol: 

CH2C1.CHC1.CH2C1. 

Phenyl  iodide  does  not  lose  iodine,  but  gives  an  addition  pro- 
duct, CeHsI.Cl^  by  the  action  of  chlorine  on  its  solution  in 
chloroform. 

In  order  to  fix  chlorine  to  alcohols,  ethers,  etc.,  which  are 


DIRECT  FIXATION  OF  GROUPS.  133. 

unsaturated,  the  method  of  procedure  is  to  pass  a  current  of 
chlorine  gas  into  their  solution  in  carbon  disulphide. 

B.  Fixation  of  Bromine  (Br). 

In  order  to  fix  bromine  to  unsaturated  gaseous  hydro- 
carbons, they  are  passed  into  liquid  bromine,  covered  with  a 
layer  of  water,  until  the  bromine  is  decolorized.  The  reaction 
may  also  be  carried  out  by  using  a  large  vessel  filled  with  the 
gas  and  provided  with  a  reservoir  of  bromine.  The  bromine  is- 
added  drop  by  drop,  and  the  flask  is  shaken  well;  the  gas  may 
be  led  in  continually  from  a  gasometer.  This  method  of  opera- 
tion is  a  good  one  for  the  fixation  of  bromine  by  ethylene. 

For  liquid  substances  bromine  water  may  be  used,  or  the 
bromine  itself  may  be  added  directly  to  the  well-cooled  substance, 
if  necessary  diluting  with  carbon  disulphide,  chloroform,  ether  ,, 
or  glacial  acetic  acid;  the  bromine  being  added  drop  by  drop 
until  the  red  color  of  an  excess  of  bromine  is  noticeable.  With 
solid  bodies  it  is  best  to  shake  their  solutions  in  one  of  the  above- 
named  solvents  with  bromine.1  If  an  excess  of  bromine  is- 
undesirable,  a  quantity  of  bromine  slightly  less  than  the  theo- 
retical is  taken.  In  order  to  avoid  a  violent  reaction,  the 
substance  is  placed  under  a  watch-glass  with  a  vessel  con- 
taining the  theoretical  amount  of  bromine,  so  arranged  that 
the  compound  is  brominated  by  the  absorption  of  the  bromine 
vapors.  If  the  substance  is  easily  oxidized,  it  is  necessary  to- 
dry  it  carefully.  There  sometimes  arise  secondary  reactions: 
iodine  compounds  not  only  fix  bromine,  but  also  exchange 
their  iodine  for  bromine;  and  the  unsaturated  acids,  in  fixing 
bromine  with  liberation  of  hydrobromic  acid,  may  give  brom- 
inated lac  tones. 

Compounds  having  the  C=C  group  can  take  up  Br2  and 
the  first  with  ease,  and  the  latter  with  more  difficulty. 


Para-nitrophenyl-propiolic  acid,  C6H4/  /^c  c  =  CCOOH' 

1  See  A.  Verigo,  Direct  Fixation  in  the  Azo-benzene  Group,  Odessa,  1871  (in 
Russian). 


134  ORGANIC  SYNTHESES. 

takes  up  Br2.  The  reaction  may  be  so  energetic  that  there  is 
sometimes  a  decomposition  of  the  body,  and,  even  by  the  regu- 
lated action  of  bromine  in  theoretical  amount,  it  is  impossible 
to  avoid  the  formation  of  some  tetrabromide. 


C.  Fixation  of  Iodine  (I). 

This  takes  place  with  more  difficulty  than  that  of  chlorine  or 
bromine.  Compounds  containing  C =C  only  take  up  I2,  and  even 
that  with  but  little  energy.  For  example,  to  combine  tolane 
C.C6H5 

with  iodine,  it  is  necessary  to  heat  their  mixture  to 
C.C6H5 

fusion.  In  order  to  fix  iodine,  either  the  gaseous  body  is  passed 
over  iodine,  or  the  substance  is  treated  with  the  latter  dissolved 
in  carbon  disulphide,  chloroform,  or  potassium  iodide.  The 
iodides  of  the  ammonium  compounds  combine  readily  with 
iodine.  Thus,  NRJ.I2  and  NR4I.I4  are  formed  by  adding  an 
alcoholic  solution  of  iodine  to  a  solution  of  NR4I. 


V.  FIXATION  OF  HALOGEN  ACIDS. 

Hydrobromic  acid  is  fixed  with  more  difficulty  than  hydri- 
odic acid,  but  less  readily  than  hydrochloric  acid.  The  action 
of  hydrochloric  or  hydrobromic  acid  takes  place  either  at  the 
ordinary  temperature  or  by  heating  in  sealed  tubes.  In  place 
of  the  aqueous  solutions  of  the  acids,  their  solutions  in  glacial 
acetic  acid  may  at  times  be  used. 

When  using  hydrobromic  acid,  it  must  not  be  forgotten 
that  there  may  also  be  a  splitting-off  of  HBr;  and,  if  the  com- 
bination contains  chlorine,  this  may  be  replaced  by  bromine. 

Concentrated  hydriodic  acid  acts  either  cold  or  hot,  either 
at  the  ordinary  pressure  or  in  sealed  tubes.  It  must  be  borne 
in  mind  that  this  acid  also  acts  as  a  reducing  agent.  Thus, 
allyl  iodide,  CaHsI,  with  hydriodic  acid,  gives  CsHe^,  which  is 
partially  reduced  to  isopropyl  iodide,  (CH3)2CHI,  and  partially 


DIRECT  FIXATION  OF  CROUPS.  135 

decomposed  into  propylene,  CH36  and  I2.  In  order  to  treat 
volatile  liquids  with  hydriodic  acid,  Lagermark  proceeds  as 
follows:  In  a  tube  is  placed  some  phosphorus  iodide,  a  glass 
capsule  containing  the  theoretical  quantity  of  water,  and  a 
small  tube  containing  the  substance;  the  tube  is  sealed  and 
placed  in  a  refrigerating  mixture,  the  capsule  is  broken,  and 
when  the  tube  is  removed  from  the  cooling  mixture  the  reaction 
is  finished. 

VI.  FIXATION  OF  WATER. 

The  fixation  of  water  to  hydrocarbons  of  the  ethylene  and 
acetylene  series  takes  place  through  the  agency  of  sulphuric 
acid.  At  first  there  is  formed  an  addition  product  with  sul- 
phuric acid  (H  and  O.SC^OH,  which  add  themselves  like  H 
and  halogens  in  the  case  of  halogen  acids),  which  is  decom- 
posed by  water  into  an  alcohol  in  the  case  of  ethylene  deriva- 
tives, and  into  an  aldehyde  or  a  ketone  (anhydrides  of  dihy- 
drates)  in  the  case  of  acetylene  compounds.  The  hydrocarbon 
is  easily  and  quickly  absorbed  by  the  sulphuric  acid  (2  to  3 
parts  of  acid  to  1  part  of  water).  It  is  necessary  to  cool  the 
mixture  well,  otherwise  there  may  be  a  polymerization. 

Sulphuric  acid  also  allows  of  the  fixing  of  water  to  com- 
pounds containing  double  or  triple  bonds  between  carbon  atoms  : 

C.C6H5  CO.C6H5 


Tolane.  Desoxy  benzoin. 

The  unsaturated  acids  of  the  acrylic  series  are  converted 
into  oxy-acids. 

Oleic  acid,  Ci8H3402,  gives  oxy-stearic  acid,  Ci8H35(OH)02. 
When  there  should  be  obtained  ^-oxy-acids  by  the  action  of 
sulphuric  acid  on  unsaturated  acids,  lactones  are  formed  instead. 

The  salts  of  mercury  permit  of  the  convenient  addition  of 
water  to  the  derivatives  of  acetylene  (method  of  KoutcherofT)  .l 

1  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  15,  p.  575. 


136  ORGANIC  SYNTHESES. 

Dilute  nitric  acid  furnishes  a  means  of  adding  water  to  the 
unsaturated  compounds.  It  is  in  this  manner  that  isobutylene 
is  converted  into  tertiary  butyl  alcohol;  croton  aldehyde, 
among  other  products,  gives  aldol.  There  may  also  be  obtained 
the  hydrate  of  terpene  by  this  method. 

The  elements  of  water  may  also  be  fixed  directly;  fumaric 
acid,  heated  with  water  to  150-180°  C.,  gives  malic  acid. 

The  oxides  and  anhydrides  of  acids  containing  the  group 

add  the  elements  of  water  by  boiling  their  aqueous  solu- 
tions, or  simply  by  exposure  to  the  air  at  ordinary  temperatures. 

The  ease  with  which  the  elements  of  water  are  affixed  de- 
creases with  increase  in  the  molecular  weight. 

Oxides  containing  a  tertiary  radical,  such  as 

CH3.CHV 

I    >, 
(CH3)2C    / 

readily  affix  water  even  in  the  cold.1    For  hydrolysis  accom- 
panied by  reduction,  see  under  Chapter  II. 

The  anhydrides  of  poly  car  boxy  lie  acids  are  converted  into 
acids,  some  by  the  action  of  water,  and  others  only  by  the  a  tion 
of  alkalies  or  alkaline  carbonates;  some  of  these  acids,  when  their 
salts  are  decomposed,  are  converted  into  anhydrides  and  water. 

Coumarin  affixes  water  through  the  medium  of  alkalies, 
and  gives  an  acid  isomeric  with  coumaric  acid,  existing  only, 
however,  in  the  form  of  a  salt;  alkalies  convert  these  salts  into 
the  corresponding  salts  of  coumaric  acid. 

Nitriles,  by  affixing  water,  are  converted  into  amides. 

R.C  E=  N  +  H20 = R.CO.NH2. 

In  neutral  liquids,  the  fixation  of  water  takes  place  slowly 
and  incompletely;  to  increase  the  speed  of  the  reaction  it  is 
necessary  to  use  an  alkaline  or  an  acid  medium.  It  is  generally 

1  Jour.  Soc.  Phys.  Chim,  Russe,  vol.  14,  p.  355;  and  Prjibuitek,  On  the  Organic 
Dioxides,  St.  Petersburg,  1887  (in  Russian). 


DIRECT  FIXATION  OF  GROUPS.  137 

customary  to  use  an  excess  of  dilute  hydrochloric  or  sulphuric 
acid,  and  to  heat,  if  necessary,  in  a  sealed  tube. 

It  must  be  borne  in  mind  that  with  an  energetic  reaction, 
as  with  acids  or  alkalies,  the  amide  in  its  turn  is  partially,  and 
sometimes  entirely,  converted  into  the  acid.  Often,  even  for 
the  preparation  of  carboxylic  acids,  in  place  of  the  amide,  the 
nitrile  may  be  used  directly.  Some  nitriles,  especially  in  the 
aromatic  series,  are  very  unstable.  Thus, 

(1)OH 

(2)  CN 

is  converted  into  salicylic  acid  simply  by  prolonged  fusion  with 
alkalies;  the  nitrile,  C6(CH3)5.CN,  is  not  converted  into  the  acid. 
The  nitriles  may  be  saponified  by  means  of  hydriodic  acid, 
but  reduction  often  takes  place.  One  of  the  best  means  of 
obtaining  hydro-atropic  acid  consists  in  saponifying  the  product 
of  the  action  of  HCN  on  acetophenone  : 

C6H5\^/OH 
CH3 

which,  on  saponification,  changes  OH  into  H  and  gives 

/OH.CO.OH. 

Oxlj 

In  order  to  convert  the  nitriles  R.CO.CN  into  amides  without 
forming  acids,  they  are  treated  in  the  cold  with  the  theoretical 
amount  of  fuming  hydrochloric  acid. 

Cyanogen  in  aqueous  solution  is  converted  almost  entirely 
into  oxamide  by  the  addition  of  a  small  quantity  of  aldehyde. 
This  reaction  may  be  explained  by  the  successive  formation  and 
destruction  of  a  dihydrate.1 

1  It  is  interesting  to  recall  that  this  fact  was  discovered  by  Liebig  while  search- 
ing for  a  synthesis  of  malic  acid  by  means  of  aldehyde  and  nascent  oxalic  acid 
(see  J.  Liebig's  and  Wohler's  Brief wechsd,  Bd.  II,  p.  78). 


I38  ORGANIC  SYNTHESES. 

Hydrogen  peroxide  also  converts  nitriles  completely  into 
amides  with  liberation  of  oxygen.  Thus : 

C6H5.CN + H202  =  C6H5.CO.NH2  +  0. 

Some  nitriles  affix  the  elements  of  water  with  particular 
ease.  If  moist  cyanogen  chloride  is  passed  through  an  ethereal 
solution  of  meta-nitraniline,  there  is  at  first  formed  a  nitrile 
which  subsequently  affixes  water  and  is  converted  into  nitro- 
phenylurea : 

(I)  N02  p  n  /N02  rN.C6H4.N02 

(3)  NH2  "         bell4  " 


Meta-nitraniline.  Nitrile.  Nitrophenyl-urea. 

The  amides,  R.CO.NH2,  by  the  fixation  of  water,  give  the 
ammonium  salts,  R.CO.ONHi.  This  reaction  has  been  con- 
sidered as  a  replacement  of  NH2  by  OH  (Chapter  I) . 

The  iso-nitriles  by  the  fixation  of  water  are  converted  into 
substituted  derivatives  of  f ormamide  • 


CH  v        0|H    OH| 
|      >N+        +        -H20 
CH/  H       H 

Some  iso-nitriles  absorb  water  with  so  much  energy  that  they 
convert  glacial  acetic  acid  into  acetic  anhydride. 

The  imides,  by  the  fixation  of  water,  give  acid  amides;  it 
is  sufficient  to  heat  them  with  baryta-water  or  lime-water,  and 
in  some  cases  with  ammonia.  The  imide  of  aspartic  acid  (see 
page  116)  gives  asparagine  : 


The  Fixation  of  Hydrogen  Peroxide  (HO.  OH).  —  This  occurs 
with  ethylene  and  gives  ethylene  glycol.    Oxidation  accom- 


DIRECT  FIXATION  OF  GROUPS.  139 

panied  by  hydration  is  another  thing  than  the  fixation  of  the 
elements  of  hydrogen  peroxide  (see  chapter  on  Oxidation) . 

The  Fixation  of  Hydrogen  Sulphide  (H2S). — This  occurs  with 
nitriles  in  the  formation  of  thio-amides.  The  nitrile  in  alco- 
holic solution  is  treated  with  ammonium  sulphydrate  at  the 
ordinary  temperature,  or  by  heating  in  sealed  tubes. 

The  Fixation  of  Sulphurous  Anhydride  (S02). — This  occurs, 
for  example,  with  zinc-ethyl : 

Zn(C2H5)  2  +  2S02  =  (C2H5.S02)  2Zn. 

For  the  preparation  of  the  sodium  salt  of  sulphinic  acid, 
see  under  Chapter  I.  Benzene  sulphinic  acid,  C6H5.SO.OH, 
occurs  as  the  result  of  the  addition  of  S02  to  C6H5  in  the 
presence  of  aluminium  chloride. 

The  Fixation  of  Bisulphites  (MHS03). — This  occurs  readily 
with  aldehydes,  the  oxide  of  ethylene  and  its  analogues. 

The  Fixation  of  Sulphuric  Anhydride  (see  page  103) . 

The  Fixation  of  Sulphuric  Acid  (see  page  135) . 


VII.  FIXATION  OF  AMMONIA  (NH3). 

Many  aldehydes  combine  with  ammonia  to  form  hydroxy 
amines : 


X\NH2' 

The  method  of  carrying  out  this  reaction  is  to  pass  a  cur- 
rent of  ammonia  gas  through  a  cooled  solution  of  the  aldehyde 
in  ether  or  chloroform,  or  to  add  to  the  aldehyde  an  alcoholic 
or  aqueous  solution  of  ammonia. 

In  the  same  manner,  the  unsaturated  acids  can  unite  with 
ammonia;  cro tonic  acid,  C4H602,  heated  in  a  sealed  tube  (100- 
115°  C.),  with  an  aqueous  solution  of  ammonia,  forms  /?-amido- 
butyric  acid,  C4H7(NH2)02. 


140  ORGANIC  SYNTHESES. 

Carbonic  anhydride  combines  with  two  molecules  of  am- 
monia, giving  the  ammonium  salt  of  carbamic  acid : 

m/NH2 

\O.NH4. 

Carbon  disulphide,  heated  with  ammonia  in  aqueous  or 
alcoholic  solution,  forms  some  sulphocyanide  and  some  sulphy- 
drate  of  ammonium,  but  these  products  may  be  considered  as 
coming  from  the  decomposition  of  the  ammonium  thiocar- 
bamate  which  is  at  first  formed : 

pc,/NH2 

V;D\    ri  ATTJ    =  v>iN  O  .li  -TL4  T~  -Cl2io . 
\O.I\Xl4 

The  iso-cyanic  esters  and  the  iso-sulphocyanides  combine 
with  ammonia  to  give  substituted  derivatives  of  urea  and 
thio-urea. 

The  nitriles  combine  with  ammonia  to  give  amidines.  For 
substituted  derivatives  of  the  amidines,  see  previous  pages. 
The  combination  of  hydroxylamine  with  nitriles  gives  amido- 
oximes  or  oximes : 

,/NH2 


VIII.  FIXATION  OF  OXIDES  OF  NITROGEN  AND  NITROSYL 

CHLORIDE.1 

By  passing  nitrous  anhydride  (arsenious  acid  and  concen- 
trated nitric  acid)  into  a  cooled  acetic  solution  of  amylene,  the 
body  C5Hio.N204  is  formed.  This  is  considered  as  a  deriva- 
tive of  trimethyl-ethylene,  and  without  doubt  has  the  formula : 

C CH3. 

O.N02.N.OH 

1  See  Wallach,  Annalen,  vols.  239,  241,  245,  and  248;  also  N.  Bunge,  On 
Nilroso  Derivatives,  Kieff,  1868  (in  Russian);  and  Jour.  Soc.  Phys.  Chim.  Russe, 
vol.  1,  p.  257. 


DIRECT  FIXATION  OF  GROUPS.  141 

With  a  nitrite  and  acetic  acid  it  is  possible  to  affix  N203. 
Terpene  yields  a  crystalline  body  (nitrosite?)  : 

' 


Nitrosyl  chloride  combines  in  the  same  manner  with  terpene 


to  give  CioHispj*      ,  when  it  is  passed  into  a  solution  of 

terpene  in  chloroform  cooled  to  10°  C.,  or  when  concentrated 
hydrochloric  acid  is  allowed  to  act  on  a  cooled  mixture  of 
terpene  and  nitrous  ether.  All  these  compounds  are  charac- 
terized by  the  ease  with  which  the  groups,  O.N02  and  O.NO, 
as  well  as  Cl,  are  replaced  by  ammonia,  amines,  potassium 
cyanide,  etc. 


IX.  FIXATION  OF  HYPOCHLOROUS  ACID  (Cl.OH).1 

Hypochlorous  acid,  in  reacting  with  unsaturated  compounds, 
gives  nearly  always  two  iso-merides.  With  acrylic  acid, 
CH2  =  CH.CO.OH,  for  instance,  it  gives: 

CH2C1.CH(OH).CO.OH  and  CH2(OH).CHC1.CO.OH. 

Often  the  OH  of  hypochlorous  acid  is  attached  to  the  same 
carbon  atom  as  the  Cl  when  reaction  with  this  acid  occurs. 

The  reaction  with  hypochlorous  acid  is  carried  out  in  the 
following  manner:  Freshly  precipitated  oxide  of  mercury  is 
mixed  with  water,  and  chlorine  is  passed  into  the  mixture  during 
constant  stirring;  then  a  fresh  quantity  of  mercury  oxide  is 
added.  This  solution  of  hypochlorous  acid  may  be  used  directly, 
or  it  is  distilled  in  a  strong  current  of  carbon  dioxide  gas  in 

1  See  P.  Melikoff,  On  Derivatives  of  the  Isomeric  Crotonic  Acids,  Odessa,  1885 
(in  Russian);  and  Jour.  Soc.  Phys.  CTiim.  Russe,  vol.  19,  p.  524;  also  C.  Refor- 
matsky,  Polyatomic  Alcohols,  Kasan,  1889  (in  Russian). 


142  ORGANIC  SYNTHESES: 

order  to  carry  off  the  chlorine.  When  the  reaction  is  finished 
the  excess  of  hypochlorous  acid  is  removed  by  the  addition  of 
sodium  hyposulphite.  Hypochlorous  acid  may  be  replaced  by 
calcium  hypochlorite  to  which  boric  acid  is  added. 

The  fixation  of  hypochlorous  acid  is  employed  especially  for 
the  preparation  of  chlorhydrins  of  the  polyhydric  alcohols. 


CHAPTER  VI. 

FIXATIONS  ACCOMPANIED  BY  A  DECOMPOSITION  OF 
THE  MOLECULE. 

I.   FIXATION  OF  WATER  (HYDRATION). 
A.  Hydration  followed  by  a  Rupture  of  Carbon  Bonds. 

MANY  of  the  aromatic  ketones,  fused  with  potash  or  distilled 
with  soda-lime,  are  decomposed  into  hydrocarbons  and  salts  of 
the  acids: 


C6H5.CO.|C6H5  +  H  OK = C6H6 + C6H5.CO.OK. 


It  is  necessary  at  times  to  employ  boiling  alcoholic  potash. 
Anthraquinone  is  converted  into  benzoic  acid  by  fusion  with 
potash  at  250°  C. : 

[4 + 2HOK = 2C6H5.CO.OK. 

Diketones  (see  page  126)  are  readily  decomposed  with  the 
addition  of  water  by  boiling  with  alkalies  or  acids,  and  yield 
ketones  and  carboxylic  acids: 

CH3-CO  ^OH=CH3.CO.OH 
"  H  ~C6H5.CO.CH3 


C6H5.CO.CH2 

A  certain  quantity  of  the  diketone  is  also  decomposed  at  the 
other  keto  group,  yielding  the  corresponding  acid  and  ketone  : 

CH3.CO.CH2  CH3.CO.CH3 


143 


144  ORGANIC  SYNTHESES. 

The  ketonic  acids,  like  aceto-acetic  acid  and  its  derivatives, 
with  concentrated  solutions  of  the  alkalies,  are  decomposed 
with  the  formation  of  carboxylic  acids.  Thus,  aceto-acetic  acid, 
or  its  ester  (which  is  saponified  during  the  reaction),  yields 
two  molecules  of  acetic  acid;  and  benzyl-ace  to-acetic  acid  (or 
its  ester)  gives  benzyl-acetic  acid  (hydrocinnamic  acid)  and 
acetic  acid: 

OH    CO.CHs  HO.OC.CH3 

TJ    nTi/  CH^.CeHs     ^TT  / 


CO.OH  2\CO.OH     ' 

In  the  same  manner,  by  heating  carboxylic  and  hydroxy- 
acids  with  dilute  sulphuric  acid,  they  are  decomposed  into  formic 
acid,  aldehydes,  and  ketones.  Some  of  them  are  decomposed 
on  heating  with  caustic  potash.  Thus,  a-oxy-isobutyric  acid: 

(CH3)2.C.OH       OH  (CH3)2.CO 

+       -H20  = 
CO.OH       H  H.CO.OH. 

Phenyl-lactic  acid,  heated  to  only  130°  C.,  is  decomposed 
into  formic  acid  and  phenyl-aldehyde  : 


C6H5.CH2.CH.OH    OH  C6H5.CH2.CHO 

+       -H20  = 
X3.0H      H  H.CO.OH. 


C 


Citric  acid  is  decomposed  in  an  analogous  manner,  when 
it  is  moderately  heated  with  concentrated  sulphuric  acid,  into 
formic  acid  and  keto-dicarboxylic  acid: 

CH2.CO.QH 

I /ICQ.OH+  H| 

I  \OJ"H      +OH| 
CH2.CO.OH 

The  latter  reactions  may  be  regarded  as  a  splitting-off  of 
formic  acid. 


FIXATIONS   WITH  DECOMPOSITION.  145 

Unsaturated  compounds,  by  the  addition  of  water  (boiling 
with  water,  dilute  acids  or  alkalies),  can  be  split  at  the  posi- 
.  tion  of  the  double  link.     Mesityl  oxide  furnishes  acetone,  and 
benzoyl-acrylic  acid  gives  aceto-phenone  and  glyoxylic  acid : 

(CH3)2C  OH    OH  (CH3)2.CO 

||          +       +       -H20  = 
CH3.CO.  CH  H       H  CH3.CO.CH3. 

C6H5.CO.  CH  H       H  C6H5.CO.CH3 

||          +        +       -H20  = 
CH          OH    OH  CHO 


C0.< 


CO.OH  CO.OH 

The  rupture  may  also  take  place  at  a  point  other  than  that 
of  the  double  link.  For  instance,  /?-trichlor-acetyl-acrylic  acid, 
by  boiling  with  baryta-water,  is  decomposed  into  chloroform 
and  f umaric  acid : 

C.C13  H 

CH.CO          OH  =  CHC13 + CH.CO.OH. 

II  *     II 

CH.CO.OH  CH.CO.OH 

For  cases  of  a  rupture  of  the  carbon  bonds  without  a  rup- 
ture of  the  molecule,  see  page  138. 

B.  Hydration  followed  by  a  Rupture  of  a  Bond  between  Carbon 

and  Oxygen. 

The  oxides  of  alcohol  radicals,  either  the  same  or  different, 
are  decomposed  by  the  fixation  of  water  when  they  are  heated 
with  dilute  mineral  acids.  Thus: 

C2H5.O.C2H5  gives  2C2H5OH. 

The  true  esters  are  only  decomposed  with  difficulty  with 
water  alone,  and  even  then  but  incompletely.  In  the  cold, 
ethyl  acetate,  CH3.CO.OC2H5,  is  slightly  decomposed  by  water; 


146  ORGANIC  SYNTHESES, 

at  100°  C.,  after  six  hours'  boiling,  the  decomposition  is  not 
very  great.  The  saponification  takes  place  more  rapidly  by 
the  action  of  acids  and  caustic  alkalies;  the  latter  are  mostly 
employed.  The  rapidity  of  the  decomposition  of  the  ester 
depends  on  its  nature,  as  well  as  on  the  acid  or  alkali  employed,, 
and  the  conditions  of  the  experiment. 

To  saponify  esters  they  are  heated  with  an  excess  of  potash 
or  soda,  baryta,  or  lime;  the  oxides  of  lead  and  magnesium 
are  also  used.  To  accelerate  the  reaction,  it  is  sometimes. 
necessary  to  add  alcohol.  The  end  of  the  reaction  is  recognized 
by  the  disappearance  of  the  ester,  which  is  difficultly  soluble 
in  water.  If  an  alkaline  solution  is  used,  the  alcohol  is  removed 
by  steam,  or  by  agitation  with  a  suitable  solvent.  The  liquid 
is  then  acidulated,  and,  if  the  acid  does  not  separate,  it  is 
removed  by  a  solvent.  If  the  acid  gives  a  difficultly  soluble 
salt,  with  a  metal  precipitable  with  hydrogen  sulphide,  such  a. 
salt  may  be  prepared  and  subsequently  decomposed  by  hydrogen 
sulphide.  For  acids  difficultly  soluble  in  water,  their  barium 
salts  may  be  prepared  and  subsequently  decomposed  with  sul- 
phuric acid. 

Esters  allow  of  a  convenient  method  for  the  preparation  of 
substituted  products  of  the  alcohols  and  acids.  Thus,  malonic 
ester,  CH2(CO.OC2H5)2,  treated  with  chlorine,  is  converted  inta 
chlor-malonic  ester,  CHC1(CO.OC2H5)2,  which  is  decomposed  in 

/PO  OTT 
the  cold  by  alkalies  into  chlor-malonic  acid,  CHC1<^  p^  OH' 

and  alcohol;  if  heat  is  employed,  the  hydroxy  compound  tar- 
tronic  acid,  CH(OH)',  is  formed. 


To  saponify  the  esters  of  the  aromatic  nitro-acids,  it  is 
necessary  to  dilute  acids,  for  the  action  of  alkalies  gives  rise 
to  azo  compounds. 

Certain  precautions  must  be  taken  with  ke  tonic  acids;  in 
certain  cases,  as,  for  example,  with  C6H5.CO.CH2.CO.OC2H5r 
it  is  necessary  to  use  sodium  carbonate  for  the  saponification, 
as  caustic  alkalies  cause  a  more  extensive  decomposition. 


FIXATIONS   WITH  DECOMPOSITION.  147 

The  anhydrides  of  the  carboxylic  acids  are  slowly  decom- 
posited  by  the  action  of  water,  and  more  rapidly  by  alkalies. 
The  anhydrides  of  the  sulphonic  acids  are  decomposed  with  a 
little  more  difficulty. 

The  carbohydrates,  C^H^On  and  C6Hi005,  take  up  water 
when  heated  with  dilute  acids,  and  are  decomposed  into  several 
other  carbohydrates.  The  glucosides  are  decomposed  in  the 
same  manner  by  hydrolysis  with  dilute  acids  and  the  action  of 
certain  ferments. 


C.  Hydration  followed  by  a  Rupture  of  a  Bond  between  Carbon 

and  Nitrogen. 

The  substituted  derivatives  of  the  amides  (anilides),  heated 
in  a  sealed  tube  with  water  or  with  concentrated  acids  (HC1 
and  H2S04) ,  combine  with  water  and  are  split  up  into  carboxylic 
acids  and  amines: 


C6H4CLNH.CO.H  +  H20  =  C6H4CLNH2  +  H.CO.OH. 

Chlor-formanilide.  Chlor-aniline. 


This  reaction  is  a  limited  one.1 

Solutions  of  alkalies  and  ammoniacal  alcohol  react  in  the 
same  manner,  but  with  more  difficulty. 

The  compounds  formed  by  the  action  of  aldehydes  on 
ammonia  and  amines  (see  page  139)  are  decomposed  by  hydroly- 
sis (heating  with  HC1)  into  their  components.  Bodies  of  the 
formula,  R.CH  =  NR',  double  their  molecule  when  heated  with 
water. 

The  decomposition  of  the  iso-nitriles  into  formic  acid  and 
amines  recalls  that  of  the  substituted  derivatives  of  form- 
anilide. 

Alkalies  hydrolyze  the  iso-cyanic  esters,  and  decompose 
them  into  carbonic  acid  and  amines.  The  iso-sulphocyanides 

1  See  Menchoutkine,  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  14,  p.  274. 


148  ORGANIC  SYNTHESES. 

behave  in  the  same  manner.  Thus,  C6H5.NCS,  heated  with 
concentrated  sulphuric  acid  (or,  for  example,  hydrochloric  acid 
acting  on  an  alcoholic  solution  of  the  body),  combines  with 
water  and  gives  C6H5.NH2,  and  COS. 


H.   FIXATION  OF  AMMONIA. 

The  decomposition  of  simple  and  compound  esters  by 
ammonia  into  amines  and  alcohols  takes  place  but  rarely : 

R.O.R  +  NH3  =  NH2R  +  R.OH. 
The  esters  of  the  ortho-  and  para-nitrophenols, 

r  H  /(I)  O.CH3      nH    r  H  /(I)  O.CH3 
CeH4\(2)  N02       and    CeH4\(4)  N02, 

heated  to  200°  C.,  with  an  aqueous  solution  of  ammonia,  give 
methyl  alcohol  and  the  corresponding  nitro-anilines. 

The  true  esters  of  the  dicarboxylic  acids  are  decomposed  by 
ammonia  into  amides  and  alcohols,  and  they  react  with  either 
one  or  two  molecules  of  ammonia. 

If  there  be  added  the  theoretical  quantity  of  an  alcoholic 
solution  of  ammonia  to  a  cooled  solution  of  oxalic  ester,  there 
is  formed  the  ester  of  oxamic  acid;  with  an  excess  of  ammonia, 
oxamide  is  obtained: 

CO.OC2H5  CO.OC2H5  CO.NH2 

CO.OC2H5  CO.NH2  CO.NH2 

Oxalic  ester.  Oxamic  ester.  Oxamide. 

Ammonia  reacts  readily  with  the  esters  of  the  substituted 
acids.  When  a-chlor-propionic  ester  is  agitated  with  ammonia,, 
it  is  converted  into  CH3.CHCLCO.NH2.  The  reaction  takes 
place  in  the  cold,  otherwise  the  chlorine  would  be  replaced  by 
NH2. 

The  anhydrides  of  the  monobasic  acids  are   decomposed 


FIXATIONS   WITH  DECOMPOSITION.  149 

more  or  less  easily  by  ammonia  with  the  formation  of  amides. 
The  imido-esters  react  very  easily  with  ammonia  to  form  ami- 
dines  : 


CHAPTER  VII. 
CONDENSATIONS. 

I.   CONDENSATION  BY  DIRECT  ADDITION. 

SOME  of  the  unsaturated  hydrocarbons  readily  combine 
with  acids  to  form  esters  of  the  alcohols.  Thus,  amylene 
(trimethyl-ethylene)  combines  with  acetic  acid  and  other  acids.1 

The  hydrocarbons,  Ci0Hi6,  heated  with  glacial  acetic  acid, 
are  converted  into  esters  of  borneol  and  its  isomerides. 

Anhydrides,  such  as  ethylene  oxide,  easily  form  with  acetic 
acid  esters  of  the  corresponding  glycols  : 

CH2.  CH2.OH 

|       >0+C2H3O.OH=  | 

CH/  CH2O.C2H30 

Ethylene  oxide.  Mono-acetic  ester  of  glycol. 

Ethylene  oxide  also  combines  with  glycol,  and  even  its  own 
molecules  polymerize. 

The  anhydrides  of  the  dibasic  acids  behave  in  the  same 
manner.  Thus,  succinic  anhydride,  by  boiling  with  absolute 
alcohol,  is  converted  into  .the  ester  of  succinic  acid  : 

CH2.COV  CH2.CO.OH 

>0+C2H5.OH=  | 
CH2.CCK  CH2.CO.OC2H5 

Aldehydes  react  with  the  anhydrides  and  chlorides  of  the 
acids  to  give  derivatives  of  the  dihydrates.  Thus: 


C6H5.CHO  +  (C2H30)  20  =  Ce 

Benzaldehyde.     Acetic  anhydride.  J3enzylidene  diacetate. 

1  See  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  20,  p.  594. 

150 


CON  DENS  A  TIONS.  I  5 1 

Some  aldehydes  combine  directly  with  the  amines  and 
amides:  cenanthylic  aldehyde  with  aniline  gives  a  body  the 
formula  of  which  is,  undoubtedly, 

C6Hl3'CH\NH.C6H5' 

Ordinary  aldehyde  gives  the  following  compound  with 
acetamide : 

'OH 


^  NH.C2H30 

The  polymerization  of  aldehyde  can  be  considered  as  the 
combination  of  several  molecules  of  aldehyde.  However,  it 
may  also  be  the  result  of  several  reactions  (formation  at  first 
of  a  hydrate,  then  removal  of  water).  Thus,  paraldehyde 
can  be  represented  as  the  combination  of  three  molecules  of 
the  dihydrate  united  with  the  loss  of  3H20: 


\>j 

i, 


CH3 
)H 

oxo 

}H.CH3. 

It  is  possible  that  the  crystalline  polymeride  of  ethylene  oxide 
is  formed  from  glycol  in  the  same  manner. 

Compounds  which  contain  several  atoms  of  carbon  and 
nitrogen,  united  with  several  bonds,  generally  combine  easily 
with  several  other  molecules. 

Thus,  cyanic  acid  and  the  iso-cyanic  esters  combine  with 
alcohols  and  various  ammonia  derivatives.  By  heating  the  fol- 
lowing ester  with  ethyl  alcohol  in  sealed  tubes  to  100°  C., 


C2H5.N=CO,    we  have 

Ethyl  ester  9f  Ethyl  ester  of 

iso-cyanic  acid.  ethyl-carbamic  acid. 


152  ORGANIC  SYNTHESES. 

With  cyanic  acid  1  the  reaction  takes  place  in  the  cold,  the 
carbamic  esters  (urethanes)  formed  by  the  excess  of  cyanic  acid 
are  converted  into  allophanic  esters  : 


Urethane.  Ethyl  allophanate. 

The  iso-cyanic  esters  combine  very  readily  with  primary 
and  secondary  amines  with  the  formation  of  substituted  deriva- 
tives of  urea.  Thus,  iso-cyanic  ester  is  converted  into  di-ethyl- 
urea  by  the  action  of  water,  the  molecule  of  ethylamine  formed 
reacting  with  the  ester  : 

C2H5.N: 


The  iso-cyanic  esters  combine  in  the  same  manner  with 
diamines  and  amides.  In  the  first  case,  according  to  the  quan- 
tity of  iso-cyanic  ester,  there  is  a  combination  between  one  or 
two  molecules : 

[H(1)C6H4(2)NH2 

^HS 

Ortho-phenylene-diamine. 


/(I)  NH2,pH  N.m    m/NH(l)C6 
CeH4\(2)  NH2+C2H*-N'CC  =CO\NH.C2H, 


or: 

CH2.NH2  CH2.NH.CO.NH.C2H5 

|  +2C2H5.N:CO=| 

CH2.NH2  CH2.NH.CO.NH.C2H5 

In  order  to  obtain  monosubstituted  ureas,  instead  of  using 
free  cyanic  acid,  potassium  cyanate  may  be  treated  with  the 
salt  of  the  amine;  the  solution  of  the  two  substances  in  water 
is  evaporated  to  dryness,  and  the  residue  is  taken  up  with  alco- 
hol. The  cyanate  formed  in  this  reaction  is  converted  so  rapidly 

1  Therefore,  according  to  this  reaction,  cyanic  acid  behaves  like  a  carbimide. 


CONDENSATIONS.  153 

by  isomerization  into  a  substituted  urea  that  one  cannot  be 
sure  of  its  formation. 

The   iso-sulphocyanides,   like   the  iso-cyanic  esters,   when 
treated  with  alcohols  and  rnercaptans,  combine  with  them: 


C6H5.N:  CS  +  C2H5.SH 


The  iso-sulphocyanides  also  combine  with  amido  com- 
pounds, and  are  converted  into  derivatives  of  thio-urea.  The 
reaction  proceeds  very  easily,  it  being  even  necessary  to  mod- 
erate it  by  diluting  the  reacting  bodies  with  a  suitable  liquid, 
alcohol,  for  example. 

Sulphocyanic  acid,  when  treated  with  amines,  gives  salts 
which  are  much  more  stable  than  the  corresponding  salts  of 
cyanic  acid.  Thus,  sulphocyan-ethyl-amine,  CNSH.NH2.C2H5, 
does  not  give  ethyl-urea  when  heated.  But  the  salts  of  the 
aromatic  amines  give  the  corresponding  thio-ureas. 

The  nitriles  combine  with  alcohols  and  mercaptans,  giving 
imido-esters  and  imido-thio-esters.  Thus: 


The  reaction  does  not  occur  by  the  direct  combination  of 
the  two  bodies;  it  is  necessary  to  pass  a  current  of  hydrochloric 
acid  gas  through  a  well-cooled  mixture  of  equi-molecular  parts 
of  the  two  bodies.  Under  these  circumstances  there  is  sub- 
sequently formed,  with  the  nitriles  of  the  aliphatic  series,  a 
compound  of  the  imido-ester  with  hydrochloric  acid.  It  is 
necessary  to  carefully  avoid  excess  of  alcohol,  or  the  following 
reaction  will  take  place  : 

CH\0  C2H5'HC1  +2C2H5OH  =CH(O.C2H5)3  +NH4C1 

Ortho-formic  ester. 

In  order  to  decompose  the  hydrochloric  acid  compound  of 
the  imido-ester,  it  may  be  treated  with  an  alcoholic  solution 


154  ORGANIC  SYNTHESES. 

of  ammonia,  or  it  may  be  dissolved  in  ether  and  shaken  with 
a  solution  of  caustic  soda. 

The  unsaturated  nitriles  take  up  HC1  at  the  same  time 

CH2 
they    form    imido-esters.      Thus,    allyl-cyanide,    ||  , 

CH.CH2.CN 
treated  with  alcohol  and  HC1,  gives 

CH3 


The  nitriles  combine  with  amines  to  form  substituted  deriva- 
tives of  the  amidines.  The  reaction  is  brought  about  by  heating 
the  nitrile  with  a  salt  of  the  amine  in  a  sealed  tube  : 


Cyanogen  (nitrile  of  oxalic  acid)  reacts  at  the  ordinary 
temperature  with  amine  compounds.  Two  NH2  groups  enter 
into  the  reaction;  that  is  to  say,  two  molecules  of  a  mono- 
amine  and  a  single  molecule  of  a  body  containing  two  NH2  or 
NH  groups.  Thus,  by  passing  cyanogen  into  an  alcoholic  or 
ethereal  solution  of  aniline,  two  molecules  of  the  latter  combine 
with  one  molecule  of  cyanogen: 


CN     C6H5.NH.C:NH 

•I     = 

CN     C6H5. 


2C6H5.NH2+  |      = 

}.NH.C:NH 


But  if  a  compound  containing  two  NH  groups  is  taken,  the 
equation  becomes: 

/NH.C6H5    CN  /N(C6H5)C:NH 

C6H5.N:C<  +|     =C6H5.N:C<(  |        . 

\NH.C6H5    CN  XN(C6H5)C:NH 

Triphenyl-guanidine. 


CON  DENS  A  TIONS.  1  5  5 

The  reaction  of  CN.CN  with  amido-benzoic  acid  takes  place 
between  an  equal  number  of  molecules. 

Cyanimide  and  its  derivatives  behave  like  a  nitrile,  and  in 
reacting  with  amido  compounds  they  yield  derivatives  of  guani- 
dine.  Thus: 


C6H5.NH2.HC1+CN.NH2=C^-NH.C6H5.HC1. 

\NH2 

The  diazo  derivatives  of  the  amido-sulphonic  acids,  by  react- 
ing with  phenols,  oxycarboxylic  acids,  or  amido  derivatives,  form 
azo  compounds  (azo-colors)  .  Thus: 

N.C6H4.S02X  N.C6H4.S02.OH 

|  >0+C6H5.OH=|| 

N  -  /  N.C6H4.OH 

The  reaction  is  carried  out  by  taking  the  theoretical  quan- 
tity of  the  diazo  compound  prepared  in  advance,  or  the  end 
product  of  the  action  of  sodium  nitrite  on  sulphanilic  acid, 

C6H4<f  r^  |T,  which  is  added  to  a  strongly  alkaline  solution  of 

\OU3-tl 

phenol;  the  intermediate  compound  which  is  formed  can  be 
transformed  by  acetic  acid  into  HO.C6H4.N:N.C6H4.S02.0K. 
In  using  amines,  it  is  better  to  take  the  hydrochloric  acid  salts. 
Other  products  are  also  obtained  at  the  same  time,  according 
to  the  equation: 


0  +  C6H5.NH2.HC1 


+  C6H5N  :  N.C1. 

Diazo-benzene  chloride. 


The  action  of  ammonia,  or  of  a  concentrated  solution  of 
potash  at  100°  C.,  on  diazo-acetic  esters,  offers  an  interesting 
case  of  condensation.  Under  these  conditions  there  is  obtained 


I56  ORGANIC  SYNTHESES. 

a  salt  (or  an  amide)  of  three  times  the  molecular  weight  of 
diazo-acetic  acid  (CHN:N.COOH)3,  which  no  doubt  has  the 
formula: 

CH.CO.OH 
/\ 


I.OC.HC 


HO.OC.HC  CH.CO.OH 

\      / 

N  =  N 

The  triazo-acid  is  decomposed  by  acids  with  the  formation  of 
diamide  (hydrazine),  formic,  and  carbonic  acids: 

(CHN :  N.CO.OH)  3  +  6H20  =  3NH2.NH2  +  3C02  +  3H.CO.OH. 

On  heating,  it  loses  water  of  crystallization,  and  then  car- 
bonic acid,  and  is  converted  into  a  body  having  the  formula, 
C3H6N6. 

Tertiary  amines  combine  with  various  chlorinated  bodies, 
with  the  formation  of  ammonium  derivatives : 

(CH3)3N+CH2C1.CH2.OH  =  (CH3)3(CH2.CH2.OH)N.C1. 

Trimethylamine.     Glycol  chlorhydrin.  Choline  chloride. 

If  the  chlorinated  derivative  contains  several  atoms  of 
chlorine,  sometimes  there  may  be  a  removal  of  halogen  acid. 
Thus,  by  the  action  of  glycerine  trichlorhydrin  on  triethylamine, 
there  is  formed  the  ammonium  compound : 

(C2H5)3(CHC1:CH.CH2)N.C1. 

The  splitting- off  of  halogen  acid  takes  place  also  when 
the  halogen  is  attached  to  a  carbon  atom  connected  with  a 


CON  DENS  A  TIONS.  157 

neighboring  atom  with  a  double  link,  as  in  the  case  of  the  propy- 
lene  bromides, 

CH3.CH:CHBr    and    CH3.CBr:CH2, 


which,  with  triethylamine,  give  allylene,  CH3.C  =  CH,  and 
triethylamine  hydrobromide. 

The  halogenated  compounds  of  the  secondary  and  tertiary 
alcohol  groups  do  not  combine  with  amines,  but  are  decom- 
posed into  hydrocarbons  and  halogen  acids. 

The  sulphur  derivatives  of  the  formula,  R2S,  combine  with 
bromine  and  iodine  compounds : l 

(C6H5.CH2)  2S  +  CH3I  =  (C6H5.CH2)  2(CH3)SL 

The  body  (C5Hn)(C2H5)S,  heated  with  methyl  iodide,  does 
not  give  a  compound  containing  three  different  groups,  but 
(CH3)3SI,  the  CH3  groups  displacing  C2H5  and  C5Hn.  The 
same  result  is  obtained  if  trie thyl-sulphine  iodide,  (C2H5)3SI,  is 
heated  with  methyl  iodide;  there  is  obtained  trime thyl-sulphine 
iodide,2  (CH3)3SI. 


1  For  the  valency  of  sulphur,  see  Gazz.  chim.  ital.,  vol.  18,  p.  62. 

2  An  analogous  substitution  by  the  methyl  group  takes  place  in  the  action 
of  methyl  alcohol  on  nitrous  ester  (Gazz.  chim.  ital.,  vol.  12,  p.  435).     In  some 
cases,  on  the  contrary,  the  methyl  group  is  displaced  by  a  radical  containing 
more  carbon  atoms: 


In  the  same  manner  the  ethyl  group  is  displaced  by  the  amyl  group  in  the  silicic 
esters: 

,+  2CSHU.OH=  Si 


158  ORGANIC  SYNTHESES. 


II.  CONDENSATION  BY  DOUBLE  DECOMPOSITION,  OR  BY 
REMOVAL  OF  GROUPS. 

A.  Formation  of  Ethers  and  Analogous  Bodies. 

(i)  With  the  Liberation  of  a  Mineral  Acid  or  of  a  Salt— 
It  is  in  this  manner  that  ordinary  ether  is  formed  when  ethyl 
bromide  or  iodide  is  heated  with  water,  or  alcohol  with  hydro- 
chloric acid  at  240°  C.  In  the  former  case  the  alcohol  formed 
at  first  reacts  on  the  halogen  compound;  and,  in  the  second 
case,  the  ethyl  chloride  which  is  formed  reacts  on  the  alcohol. 
Sulphuric  acid  with  alcohol  also  produces  ether  (the  ordinary 
method  of  producing  this  compound) . 

In  order  to  obtain  mixed  ethers  (the  tertiary  alcohols  of  the 
aliphatic  series  do  not  yield  any),  very  often  recourse  is  had  to 
the  action  of  halogen  derivatives  on  the  metallic  compounds 
of  the  alcohols  (alcoholates  and  phenates) : 

R.O.Na  +  R'Cl  =  R.O.R' + NaCl. 

To  a  solution  of  sodium  alcoholate  in  alcohol  (by  dissolving 
sodium  in  alcohol)  there  is  directly  added  the  theoretical  quan- 
tity of  the  halogen  compound,  and  the  reaction  is  finished  by 
heating;  or  the  alcoholate  may  be  isolated  by  distilling  off  the 
alcohol,  and  then  it  is  allowed  to  react  with  the  halogen  com- 
pound. The  phenates,  obtained  by  evaporation  of  an  alkaline 
solution  of  phenol,  are  treated  with  the  halogen  compound  or 
with  alkyl  acid  sulphate. 

The  simple  or  mixed  ethers  can  also  be  prepared  by  heating 
(in  a  sealed  tube  if  necessary)  together  potash,  alcohol,  and 
the  halogen  compound.1 

With  the  aliphatic  alcohols  there  are  often  formed  unsat- 
urated  hydrocarbons  as  secondary  products. 

1  To  obtain  the  ethers  of  phenols  the  alcohol  is  added,  together  with  the  corre- 
sponding hydrochloric  acid  ester. 


CON  DENS  A  TIONS.  159 

Compounds  rich  in  hydroxyl  groups  readily  give  several 
ethers,  principally  the  neutral  ethers.  Hydroquinone,  on 
boiling  with  an  excess  of  potash  and  methyl  iodide,  gives 
dimethyl  ether;  glycerin,  with  propyl  iodide  and  potash,  fur- 
nishes C3H5(OC3H7)3. 

In  order  to  substitute  only  a  part  of  the  hydroxyl  groups, 
it  is  necessary  to  take  the  theoretical  quantities  of  potash  and 
RI  or  sulphovinate. 

Even  when  oxycarboxylic  acids,  oxyaldehydes,  and  other 
compounds  containing  the  OH  group,  are  heated  with  potash 
and  RI  or  R.OH,  they  are  converted  into  the  corresponding 
ester. 

Bodies  rich  in  halogen  react  with  several  molecules  of  alcohol- 
ates.  Thus,  ethylidene  bromide,  CH3.CHBr2,  is  converted  into 
acetal  (ether  of  a  dihydrate),  and  chloroform  into  orthoformic 
ether  (ether  of  a  trihydrate).  If  the  halogen  atoms  are  not 
fixed  to  one  and  the  same  carbon  atom,  but  to  neighboring 
atoms,  there  may  be  partial  or  total  substitution: 


CH2.C1  CH2C1 

+C2H5.ONa  =  |  +NaCl. 

HC1.0C2H5  CH(OC2H5)2 

Chlor-acetal. 


X-/. 

i 


There  may  be  a  simultaneous  splitting-off  of  halogen  acid. 
The  tribromhydrin  of  glycerin,  by  the  action  of  a  solution  of 
caustic  potash  in  alcohol,  gives  the  ether  of  propargylic  alcohol : 

CH2Br  CH 

CH.Br + 3KO.C2H5  =  C  +  3KBr  +  2C2H5OH. 


2.Br  CH2.O.C2H5  . 

Tribromhydrin.  Propargylic  ether. 

To  the  reactions  above  enumerated  must  be  added  that 
between  a  halogen  compound,  RI  in  particular,  and  a  metallic 
oxide,  M20.  Generally,  silver  oxide  is  used;  sometimes  there 


160  ORGANIC  SYNTHESES. 

may  be  a  removal  of  hydriodic  acid  and  a  replacement  of  I 
by  OH.* 

The  true  esters  are  obtained  very  easily  by  the  action  of 
acid  chlorides,  which  readily  react  with  OH  groups.  The 
chlor-acid  chlorides  behave  in  the  same  manner  : 


CH3.CHC1.COC1+C2H5.OH=CH3.CHCLCO.OC2H5 


In  this  reaction  it  is  only  the  chlorine  of  the  CO.C1  group 
which  reacts.  The  chloride  of  chlor-formic  acid  (carbonyl 
chloride,  COC^)  does  not  give  the  same  reactions  on  account  of 
its  particular  constitution;  with  alcohol  in  the  cold,  it  gives 
esters  of  chlor-formic  acid,  which,  by  boiling  with  alcohols,  are 
converted  into  esters  of  carbonic  acid  : 


The  chlorides  of  the  dicarboxylic  acids  exchange  only  one  of 
their  chlorine  atoms  for  OR. 

Compounds  containing  several  OH  groups  will  react  with 
several  molecules  of  acid  chlorides.2  In  the  aliphatic  series, 
the  hydrochloric  acid  which  is  liberated  can  also  enter  into 


1  By  the  use  of  acid  chlorides  the  hydrogen  of  the  hydroxyl  group  of  oximes 
may  also  be  replaced.      Thus,  acetoxime  (GH3)2C:N.OH,  with  benzoyl  chloride, 
gives    (CH3)2C:N.O.CO.C6H5.      From    the  aldoximes   may  readily  be  obtained 
the  acids  of  which  they  consist,  through  often,  in  their  place,  decomposition 
products  are  formed: 

C6H6.CH  :NO.CO.CH3=  C6HS.CN+  CH3.CO.OH. 

In  the  oximes,  the  hydrogen  of  the  hydroxyl  group  may  easily  be  replaced 
by  an  alcoholic  radical.  If  benzaldoxime  and  CH3I  are  added  to  an  alcoholic 
solution  of  caustic  soda,  there  is  formed  C6H5.CH:NO.CH3. 

2  The  reaction  with  the  acid  chlorides,  particularly  C6H6.CO.C1,  is  a  means  of 
determining  the  presence  of  the  hydroxyl  (OH)  group.     The  product    of    the 
reaction,  freed  from  excess  of  benzoyl  chloride,  is  decomposed  with  standard 
potash,  and  the  excess  of  the  latter  determined  by  titration. 


CON  DENS  A  TIONS.  1 6 1 

the  reaction  and  convert  OH  into  Cl.    Dextrose  with  acetyl 
chloride  gives  an  aceto-chlorhydrin : 1 

C6H70(OH)5 >    C6H70(O.C2H30)4C1. 

Dextrose.  Aceto-chlorhydrin. 

In  certain  cases,  in  order  to  obtain  the  esters  the  acid 
chloride  is  allowed  to  act  on  an  alcoholate.2  Thus,  the 
esters  of  cyanic  acid,  N=C.OC2H5,  are  obtained  by  the  action 
of  cyanogen  chloride  on  an  alcoholate  dissolved  in  an  excess 
of  alcohol. 

The  esters  are  also  formed  by  the  reaction  of  the  salts  of 
the  carboxyl  acids  (and,  in  the  same  manner,  the  thio-acids) 
and  their  derivatives  with  halogen  compounds.3  Generally,  the 
chlorine  or  bromine  compound  is  allowed  to  react  on  the  alkaline 
salt  of  the  acid,  or  the  iodine  derivative  on  the  silver  salt. 

The  silver  salt,  moistened  with  the  corresponding  acid,  is 
gradually  heated  with  RI;  a  certain  quantity  of  the  product 
escapes  during  the  reaction,  but  this  may  be  avoided  by  taking 
an  excess  of  silver  salt.  In  certain  cases  it  is  necessary  to  dilute 
the  reagents  in  ether  in  order  to  moderate  the  reaction. 

The  anhydrides  of  the  acids  are  obtained  with  difficulty  by 
the  action  of  acid  chlorides  on  the  acids.  Thus,  the  reaction, 

C6H5.CO.C1 + C6H5.CO.OH  =  C6H5.CO.O.CO.C6H5  +  HC1, 

only  takes  place  by  heating  in  a  sealed  tube,  and  even,  in  any 
case,  only  about  50  per  cent,  of  the  theoretical  yield  is  obtained. 

1  See  A.  Colley,  On  Grape  Sugar,  Moscow,  1869  (in  Russian). 

2  The  chlorides  of  the  sulphqnic  acids,  R.SO2.C1,  behave  like  those  of  the 
carboxylic  acids;   with  alcohols  and  the  alcoholates  they  yield  the  corresponding 
esters.     Sometimes  it  is  sufficient  to  evaporate  the  alcoholic  solution  to  obtain 
the  ester;   but  in  other  cases,  a  prolonged  boiling  is  required  or  zinc  dust  is  used, 
as,  for  example,  in  the  reaction  of  R.SO2.C1  on  the  phenols.     The  action  of  the 
chloride  of  the  sulphonic   acids   may  be    moderated   (particularly  CgH^SO^Cl) 
by  dissolving  them  in  ether,  or  by  adding  the  alcoholate  in  an  excess  of  alcohol. 

3  In  the  same  manner  are  produced  the  esters  of  the  dihydric  alcohols.      See 
~L  Tuttschew,  On  Glycols  in  General  and  on  a  New  Compound,  Carvol-dibenzoate, 
St  Petersburg,  1858  (in  Russian). 


1  62  ORGANIC  SYNTHESES. 

A  good  method  of  obtaining  the  anhydrides  is  the  action 
of  dehydrated  oxalic  acid  on  acid  chlorides,  or  the  action  of 
the  latter  on  the  salt  of  the  acid.1 

In  place  of  using  the  ready-  prepared  chloride,  the  direct 
action  of  phosphorus  oxychloride  (1  molecule)  on  the  salt  of  the 
acid  (4  molecules)  may  be  used.  The  reaction  takes  place  in 
two  phases: 

2CH3.CO.OM  +  PC130  =  PM03  +  MCI  +  2CH8.CO.C1, 
2CH3.CO.C1  +  2CH3.CO.OM  =  2MC1  +  2CH3.CO  .  O.CO.CH3. 

The  anhydrides  of  the  acids  are  also  obtained  by  the  action 
of  the  acid  chloride  on  the  nitrate  of  lead  or  silver,  and  also 
by  the  action  of  carbonyl  chloride  on  the  sodium  salt  of  the  acid  : 

2C2H3O.ONa  +  COC12  =  (C2H30)  20  +  2NaCl  +  C02. 

Sodium  acetate.       Carbonyl        Acetic  anhydride. 
chloride. 

(2)  Formation  of  Ethers,  etc.,  with  Liberation  of  Water.  — 
The  direct  formation  of  simple  or  mixed  ethers  (oxides  of 
the  alcoholic  radicals),  with  elimination  of  water,  takes  place 
only  with  difficulty  and  always  incompletely.  With  ethyl 
alcohol,  the  ether  is  obtained  by  energetic  heating  with  a  sul- 
phate or  a  chloride,  although  it  may  be  considered  that  .  the 
ether  is  formed  through  the  action  of  the  acid  liberated  in  the 
decomposition  of  the  salt. 

Benzhydrol,  (Cells)  2.CH.  OH,  is  readily  converted  into  the 
corresponding  ether,  [(C6H5)2CH]20;  the  alcohol  of  fluorene, 


CeKjv 
|         >C 


/eiy        \ 

H.OH,  gives  the  ether,  (  |         >CH  0, 
\C6H/       /2 


by  simple  fusion;   the  alcohol  of  cumene,  C6H4(C3H7)CH2.OH, 
containing  traces  of  inorganic  substances  (one  or  two  drops  of 

1  With  the  chlorides   of  the  polycarboxylic  acids  there  may  be  a  secondary 
reaction  on  account  of  the  splitting  off  of  water. 


CONDENSATIONS.  163 

sulphuric  acid,  for  example),  is  decomposed  on  distilling  into 
the  ether  [CeH^CaH^CHakO  and  water.  (For  the  ethers  of 
the  dihydrates,  see  previous  pages.) 

The  methods  employed  in  the  aliphatic  series  do  not  always 
hold  with  the  phenols,  and  it  is  necessary  to  use  dehydrating 
agents.  Thus  phenol,  heated  with  zinc  chloride,  gives  a  small 
quantity  of  the  ether  (C6H5)20.  Resorcin,  at  180°  C.,  with 
fuming  hydrochloric  acid,  gives  the  corresponding  ether  of 
resorcin,  (C6H4.0H)20. 

The  anhydrides  of  the  mono  carboxylic  acids  are  obtained 
with  difficulty,  even  by  the  action  of  strong  dehydrating  agents. 
Glacial  acetic  acid  with  phosphoric  anhydride  gives  a  small 
quantity  of  acetic  anhydride.  For  its  preparation  there  may 
be  employed  an  iso-nitrile  (see  page  138). 

The  formation  of  the  esters  by  the  use  of  alcohols  and  acids 
takes  place  much  better,  but  the  reaction, 

R.CO.OH + R'.OH  =  R.CO.OR' + H20, 

is  never  complete ;  as  soon  as  there  is  an  equilibrium  established 
between  the  decomposition  of  the  acid  ester  and  the  water  on 
the  one  hand,  and  the  formation  of  the  ester  on  the  other  hand, 
the  reaction  stops. 

The  point  of  equilibrium  depends  on  the  nature  of  the  alcohol 
and  ester.  It  is  necessary  to  use  an  excess  of  the  reagents  and 
to  remove  the  water  which  is  formed  at  the  same  time  as  the 
ester.  This  is  usually  accomplished  by  passing  a  current  of 
dry  hydrochloric  acid  gas  through  a  mixture  of  the  alcohol 
and  acid,  and  heating  from  time  to  time. 

The  esters  of  the  phenols  are  formed  by  the  action  of  phos- 
phorus oxychloride  on  a  mixture  of  the  phenol  and  acid,  there 
being  a  liberation  of  hydrochloric  acid. 

With  polyhydric  alcohols,  according  to  circumstances,  it  is 
possible  to  replace  one  or  more  hydrogen  atoms  of  the  OH 
groups. 

The  anhydrides  of  the  acids  react  more  readily  than  the 


164  ORGANIC  SYNTHESES. 

acids  with  alcohols,  even  without  heating  and  in  the  absence 
of  dehydrating  agents;  and  in  the  majority  of  cases  the  reac- 
tion is  complete.  They  are  employed  in  the  preparation  of 
esters  to  replace  the  acid  chlorides  when  the  latter  react  with 
difficulty  or  give  secondary  products.  In  the  case  of  acetic 
anhydride,  its  action  is  increased  by  the  addition  of  dehydrated 
sodium  acetate. 

The  acetals  (ethers  of  the  dihydrates)  are  obtained  by  heat- 
ing aldehydes  with  alcohols: 

CH3.CHO  +  2C2H5.OH  =  CH3.CH(OC2H5)  2  +  H20. 

The  reaction  takes  place  at  100°  C.,  if  to  a  mixture  of  the 
aldehyde  (1  part),  and  the  alcohol  (3  parts),  there  is  added  glacial 
acetic  acid  (  J  part)  ;  as  a  secondary  product  there  is  formed 
some  acetic  ester,  which  is  removed  by  heating  in  a  closed 
vessel  with  caustic  potash  ;  the  acetal  formed  being  dehydrated 
with  calcium  chloride.  A  better  yield  of  acetal  is  obtained 
by  passing  a  current  of  non-inflammable  hydrogen  phosphide 
into  a  mixture  of  alcohol  and  aldehyde,  cooled  to  21°  C. 

The  polyhydric  alcohols  behave  in  the  same  manner  with 
aldehydes  as  the  monohydric  alcohols. 

Acetals  are  generally  obtained  by  the  oxidation  of  the  cor- 
responding alcohols.1 

(3)  Formation  of  Esters,  etc.,  with  Liberation  of  Ammonia 
or  Nitrogen.  —  The  amides  of  certain  acids  can  be  converted 
into  esters  with  liberation  of  ammonia  by  the  action  of  alco- 
hols in  the  presence  of  acids.  Thus  : 

NH2.CHO  +  C2H5.OH  +  HC1  =  CHO.OC2 


By  boiling  urea  with  a  large  quantity  of  propyl  alcohol,  we 
have: 


1  By  the  oxidation  of  a  mixture  of  methyl  and  ethyl  alcohols,  there  is  ob- 
tained, not  the  mixed  acetal,  CH3.CH(OCH3)(OC2H5),  but  a  mixture  of  methyl 
and  ethyl  acetals. 


CONDENSATIONS.  165 

For  the  preparation  of  ortho-esters  (ortho-formic  ester)  y 
by  the  reaction  of  imide-ethers  on  alcohols,  see  page  153. 

The  diazo-compounds  may  be  converted  into  esters  under 
certain  conditions.  Thus,  by  decomposing  the  aromatic  diazo- 
derivatives  with  acetic  acid,  the  acetic  esters  of  the  phenols  are 
obtained  : 


CeH4\N  :  N.S04H 


The  esters  of  diazo-acetic  acid,  on  boiling  with  alcohol,  give 
the  esters  of  e  thy  1-gly  colic  acid  : 


CH<||  CH2.OC2H5 

|     XN        +C2H5.OH=| 
CO.O.C2H5  CO.OC2H5 


B.  Preparation  of  Compounds  containing  Sulphur. 

Sulphuretted  compounds  may  be  obtained  by  the  action  of 
chlorine  compounds  (or  salts  of  the  sulphonic  acids)  with  the 
corresponding  mercaptides,  RSM  l : 

CC14 + 4C2H5.SNa  -  C  (SC2H5)4 + 4NaCL 

Sulphuretted  compounds  containing  two  similar  R  groups 
are  obtained  directly  by  the  action  of  the  chlorine  compounds 
on  potassium  sulphide,  K2S. 

The  tertiary  halogen  derivatives,  as,  for  example,  tertiary 
iso-butyl  iodide  (CH3)3C.I,  do  not  form  sulphur  compounds  with 
potassium  sulphide,  for  generally  there  is  a  decomposition  of 
the  halogen  compounds.  Among  the  aromatic  halogen  deriva- 

1  The  acid  chlorides  react  with  the  mercaptans  themselves.  Thus,  CgH^SH 
heated  with  acetyl  chloride,  CH3.CO.C1,  liberates  hydrochloric  acid  and  gives 
the  ester  of  thioacetic  acid,  CH3.CO.S.C2H5. 


166  ORGANIC  SYNTHESES. 

tives  there  are  some  in  which  the  halogen  is  replaced  by  HS 
by  treatment  with  potassium  sulphide. 

Sulphur  compounds  similar  to  those  of  the  dihydrates  are 
formed  by  the  condensation  of  aldehydes  and  ketones  with 
mer  cap  tans  and  thio-gly  collie  acid.  By  passing  hydrochloric 
acid  into  a  mixture  of  mercaptan  and  acetone,  there  is  formed 
aceto-ethylmercaptol  :  1 

(CH3)  2CO  +  2C2H5.SH  =  (CH3)  2C/^p2^5  +  H20. 


Compounds  containing  S2  are  formed  by  the  action  of  halogen 
compounds  on  M2S2;  and  by  the  removal  of  hydrogen  from 
mercaptans  and  thio-acids  with  the  aid  of  oxidizing  agents 
(gaseous  oxygen,  ferric  chloride,  chromic  and  nitric  acids,  hydro- 
gen peroxide,  etc.);  thus: 


is  converted  into  |  . 

C6H5.S 

The  preparation  of  compounds  containing  S2,  by  the  action 
of  sulphuric  acid  on  mercaptans,  takes  place  according  to  the 
following  equation  : 

2C2H5.SH  +  H2S04  =  (C2H5)  2S2  +  S02  +  2H20. 

By  the  action  of  iodine  on  C2H5.SNa,  the  disulphide  of 
phenyl,  (C6H5)2S2,  is  formed. 

The  sulphones,  R.S02.R,  are  formed  by  heating  an  aromatic 
sulphonic  acid  with  an  aromatic  hydrocarbon  in  the  presence 
of  a  dehydrating  agent,  such  as  phosphoric  anhydride;  they 
are  also  obtained  by  the  action  of  sulphuric  anhydride  on  a 
hydrocarbon,  and  by  the  action  of  sulphochlorides  or  aromatic 
hydrocarbons  in  the  presence  of  aluminium  chloride.  Thus: 

C6H5.S02C1+C6H6  =  S 


1  By  oxidizing  with  potassium  permanganate  there  is  formed  a  disulphone, 
(CH3)2C(SO?.C2H5)2,  called  sulphonal,  which  has  a  physiological  action  some- 
what analogous  to  chloral. 


CONDENSATIONS.  167 

The  sulphones  are  also  obtained  by  the  action  of  halogen 
compounds  on  the  salts  of  the  sulphinic  acids: 


C2H5.S02Na  +  C2H5.Br  =  S02p25  +  NaBr  . 


For  the  preparation  of  sulphones  by  the  oxidation  of  sulphur 
compounds,  see  under  direct  fixation  of  oxygen. 

C.  Formation  of  Compounds  containing  Nitrogen. 

(1)  AMMONIA  DERIVATIVES. 

(a)  Derivatives  formed  with  Liberation  of  Halogen  Acids  or 
other  Acids  or  Salts.  —  The  amines  react  with  halogen  compounds 
in  the  same  manner  as  ammonia  (see  page  93),  and  are  converted 
into  secondary  amines,  and  even  tertiary  amines,  with  an  excess 
of  the  halogen  compound. 

The  secondary  iodides,  in  their  action  on  amines,  yield  hydro- 
carbons together  with  secondary  amines.  For  example,  isopropyl- 
iodide  (CH3)2CH.I,  with  isopropyl-amine  (CH3)2CH.NH2,  is 
converted  into  [(CH3)2CH]2.NH  and  propylene,  CH3.CH:CH2. 
In  order  to  separate  the  substances  so  formed,  the  mixture 
is  treated  with  nitrous  acid,  and,  by  the  nitrosamine  thus  pro- 
duced, the  secondary  amine  is  removed. 

The  amido-acids  react  with  chlorine  compounds,  and,  accord- 
ing to  the  conditions  of  the  reaction,  there  is  a  substitution  of 
one  or  two  atoms  of  hydrogen  in  the  NH2  group.  By  heating 

one  molecule  of  para-amido-benzoic  acid,  CeH^  ,^  QQ 

with  a  solution  (3  mols.)  of  caustic  soda  in  alcohol  and  two 
molecules  of  methyl  iodide,  there  is  obtained  dimethyl-para- 

•A    u         •          -A    n  TI  /(I)   N(CH3)2 
amido-benzoic  acid,  CetUC   )^<  ^Q  QJJ  . 

Amines  with  cyanogen  chloride  give  substituted  cyanamines. 
The  reaction  is  brought  about  by  passing  cyanogen  chloride 
into  an  ethereal  solution  of  the  amine  : 

CNC1+  C6H5.NH2  =  C6H5.NH.CN  +  HC1. 


1  68  ORGANIC  SYNTHESES. 

With  an  excess  of  amine,  a  guanidine  substitution  product  is 
formed. 

The  acid  chlorides  react  energetically  with  amido  compounds, 
as  do  also  the  sulpho-chlorides,  R.S02.C1  : 

CH3.S02.C1  +  2C6H5.NH2  =  CH3.S02.NH.C6H5  +  C6H5.NH2HCL 

The  substituted  amides  so  formed  (for  example,  the  anilides) 
do  not  present  a  basic  character. 

As  to  the  manner  in  which  the  acid  chlorides  behave  with 
ortho-diamines,  see  page  117. 

Carbonyl  chloride,  COC12,  with  secondary  diamines,  behaves 
in  the  same  manner  as  other  acid  chlorides;  there  is  a  substitu- 
tion of  H  by  COC1,  and  the  formation  of  special  chlorides  derived 
from  urea,  which  in  their  turn,  when  heated  with  the  diamine, 
give  substituted  derivatives  of  urea.  Thus  : 

(C6H5)  2NH  +  COC12  =  (C6H5)  2N.COC1  +  HC1. 
(C6H5)  2N.COC1  +  (C6H5)  2NH  =  CCX  +  HCL 


The  primary  amines  of  the  aromatic  series  yield  disub- 
stituted  ureas,  which  in  their  turn,  when  heated  a  long  time 
with  carbonyl  chloride,  give  isocyanic  esters  : 


O\NH  CeH 


+  COCl2  =  2C6H5-NCO  +  2HC1. 


Phenyl-isocyanate,  C6H5.NCO,  may  be  obtained  in  the  same 
direct  manner  by  passing  carbonyl  chloride  over  the  fused  chlo- 
ride of  the  amine  : 

C6H5.NH2.HC1  +COC12  =  2C6H5.NCO  +3HC1. 

In  the  aliphatic  series,  the  isocyanic  esters  are  obtained  by 
the  distillation  of  RI  or  R.HS04  with  the  cyanates. 


CONDENSATIONS.  169 

(b)  Ammonia  Derivatives  formed  with  Liberation  of  Water. 

— The  primary  aromatic  amines  become  secondary,  and  the 
secondary  tertiary,  when  they  are  heated  with  alcohols  of  the 
aliphatic  series.  Thus: 

C6H5.NH2  +  CH3.OH  =  C6H5.NH.CH3  +  H20. 

The  higher  alcohols  of  the  aliphatic  series,  with  dehydrating 
agents,  give  substituted  derivatives  of  the  R  group  in  the 
hydrogen  of  the  benzene  nucleus. 

The  phenols  react  with  the  amines  when  heated  to  250- 
300°  C.  in  the  presence  of  the  chlorides  of  zinc  or  calcium.  The 
diphenols  react  more  readily;  for  example,  resorcin  or  hydro- 
quinone  with  aniline  react  at  300°  C.  with  dehydrating  agents: 

C6H4(OH)  2  +  C6H5.NH2  =  C6H4(OH)  NH.C6H5  +  H20. 

With  ortho-diamines,  pyrocatechin  gives  phenazines;  for 
example,  when  heated  for  some  time  with  ortho-phenylene- 
diamine,  it  gives  the  phenazine  identical  with  the  azo-phenylene, 
Ci2H8N2,  of  Rasenack  and  Glaus: 


CoH.4\       yCoH.4. 
\N/ 

In  this  case,  there  is  a  removal  of  H2  at  the  same  time  as  a 
removal  of  water. 

The  a-oxynitriles  react  easily  with  amido  compounds. 

If  the  cyanhydrate  of  methyl-salicyl  aldehyde  is  heated 
with  an  alcoholic  solution  of  ammonia  to  60-70°  C.,  there  is 
at  first  obtained  the  nitrile  of  an  amido-acid,  which  then  reacts 
again  on  the  cyanhydrin  in  excess,  as  indicated  by  the  following: 

'OCH3  /OCH3 


\OH  NH2 


170  ORGANIC  SYNTHESES. 

The  carboxylic  acids  readily  react  with  amines  to  form  at 
first  salts,  which  by  loss  of  water  give  substituted  amines. 

If  an  aqueous  solution  of  methylamine  and  formic  acid  is 
distilled,  there  is  formed  methyl-formamide : 

HCO.OH + CH3.NH2  =  HCO.NH.CH3 + H20. 

Benzyl-acetamide  is  obtained  by  heating  benzylamine  with 
glacial  acetic  acid;  acetanilide  is  obtained  by  a  similar  process  1 
(see  page  175).  By  heating  equal  molecules  of  acid  and  amine 
the  reaction  is  not  complete,  for  the  water  formed  causes  the 
decomposition  of  the  substituted- derivatives  of  the  amine  (see 
page  147) ;  in  order  to  increase  the  yield,  it  is  necessary  to  take 
an  excess  of  acid.  In  certain  cases,  the  reaction  is  made  more 
complete  by  heating  in  sealed  tubes,  or  by  the  use  of  dehy- 
drating agents.  For  example,  in  order  to  prepare  chlor-acet- 
anilide,  the  chlor-acetate  of  aniline  is  treated  with  phosphoric 
anhydride : 

C6H5.NH2.HO.OC.CH2C1  -  H20 = C6H5.NH.CO.CH2.C1. 

Without  this  assistance  there  would  probably  be  formed  phenyl- 
glycocoll,  CH2(NH.C6H5)CO.OH,  with  liberation  of  hydro- 
chloric acid. 

Diamido  compounds  react  with  either  one  or  two  molecules 
of  acid. 

For  the  manner  in  which  the  ortho-diamines  behave  with 
acids,  see  page  117. 

Dicarboxylic  acids  form  two  series  of  derivatives,  according 
to  the  number  of  molecules  taking  place  in  the  reaction.  By 

1  The  substituted  derivatives  of  the  amides  can  be  obtained  by  the  action 
of.  the  amines  on  the  esters,  alcohol  being  liberated.  The  substituted  derivatives 
of  the  aromatic  amines  (anilides)  are  formed  in  some  cases  by  the  action  of" 
phenol  on  the  amine: 

C10H7(/?)OH+CH3.CO.NH2=CH3.CO.NH.C10H7+H20. 


CON  DENS  A  TIONS.  1 7 1 

heating  aniline  with  an  excess  of  oxalic  acid,  the  derivatives  of 
oxamide  are  obtained : 


CO.OH  CO.NH.C6H5 

|  +2C6H5.NH2=| 

CO.OH  CO.NH.C6H5 


+H20. 


With  equal  molecules  of  acid  and  base,  a  derivative  of  oxamic 
acid  is  formed : 

CO.OH  CO.NH.C6H5 

|  +C6H5.NH2=|  +H20. 

CO.OH  CO.OH 

Some  substituted  derivatives  of  the  amido-acids  at  the 
temperature  at  which  they  are  formed  decompose  into  water 
and  a  substituted  derivative  of  an  imide : 

CH2.CO.NH.C6H5  CH2.COV 

|  -H20=|  >N.C6H5. 

CH2.CO.OH  CH2.CO/ 

The  anhydrides  of  the  acids  behave  in  the  same  manner 
as  the  acids  when  treated  with  amines.  They  are  used  when 
the  NH2  group  is  substituted  with  difficulty  in  the  acid  radical, 
or  when  it  is  necessary  to  avoid  a  long  heating,  which  is  neces- 
sary when  the  acid  is  used.  The  reaction  with  anhydrides  can 
be  moderated  by  using  a  suitable  solvent,  or  it  may  be  increased 
by  means  of  a  dehydrating  agent,  such  as  fused  sodium  acetate. 
With  amido-phenol,  the  acid  group  of  the  anhydride  does  not 
only  act  on  the  NH2  group,  but  also  on  the  OH  (see  page  164). 
For  ortho-amido-phenol,  see  page  117. 

The  aldehydes  react  with  one  or  two  molecules  of  amido 
compounds,  with  the  liberation  of  water  and  the  formation  of 
a  single  or  double  bond  between  the  carbon  and  nitrogen.1 
Thus  benzaldehydes  react  with  aniline  as  follows : 

C6H5.CHO + NH2.C6H5 = C6H5.CH :  N.C6H5 + H20. 

1  For  the  action  of  aldehydes  on  aromatic  amines,  see  p.  196. 


I72  ORGANIC  SYNTHESES. 

Ordinary  aldehyde  behaves  in  the  same  manner  with  meta- 
amido-benzoic  acid,  forming: 

(1)  CO.OH 
(3)  N:CH.CH3' 

There  may  at  first  be  formed  an  addition  product,  R.CH(OH). 
NH.R'  (see  page  151),  which  is  then  decomposed  with  loss  of 
water. 

Ordinary  aldehydes  react  with  two  molecules  of  primary 
or  secondary  amines.1  On  mixing  one  molecule  of  aldehyde 
with  two  molecules  of  aniline,  the  following  reaction  takes 
place : 

CH3.CHO + 2C6H5.NH2 = CH3.CH(NH.C6H5)  2 + H20. 

The  aromatic  aldehydes  condense  with  ortho-diamines  with 
liberation  of  2H20  (2  mols.  of  aldehyde  and  1  mol.  of  ortho- 
diamine).  The  compound  so  formed  is  not  a  simple  substi- 
tution of  the  hydrogen  of  the  ammonia  by  2R";  it  is  called 
aldehydine,  and  is  a  derivative  of  the  amidines  (see  page  154). 
Thus,  by  the  action  of  benzaldehyde  on  ortho-phenylene- 
diamine,  we  obtain  benzaldehydine : 


C6H       \ 

=  C.C6H5 


In  this  reaction  there  is  a  simultaneous  reduction  and  oxida- 
tion of  benzaldehyde. 

Glyoxal,  and   compounds    containing    two   CO  groups    in 


1  The  formation  of  such  compounds  as  ammonia-acrolein  and  hydrobenzamide 
can  be  explained  by  admitting  that  they  are  the  result  of  a  condensation  between 
the  aldehyde  and  the  addition  products  of  ammonia: 

+ C6H5.CHO=   «» 


CON  DENS  A  TIONS.  1 7  3 

the  ortho  position  (benzil,  phenanthraquinone,  etc.),  combine 
with  ortho-diamines  to  give  quinoxalines: 1 


CHO     H2N  CH=Nv 

>C6H4+2H20. 
=  N/ 

Quinoxaline. 


|        + 
CHO     H2N 


Bodies  containing  the  CO  group  react  in  the  same  manner  as 
aldehydes  2  with  bodies  containing  NH2.  The  anilides,  heated 
with  amines  and  phosphorus  trichloride,  give  substituted  deriva- 
tives of  the  amidines  : 

CH3.CO.NH.C6H5  +  C6H5.NH2  =  CH3.C/5  +  H20. 


As  the  anilide  is  prepared  by  the  action  of  the  acid  on  the  amine, 
it  is  possible  to  obtain  the  substituted  derivatives  of  the  amidines 
by  heating  together  the  amine  and  acid  with  phosphorus  tri- 
chloride. 

Urea  condenses  (with  liberation  of  water)  with  various 
compounds.  By  heating  it  with  isodialuric  acid  (obtained  by 
the  conversion  of  the  condensation  product  of  aceto-acetic 

1  Hinsberg  (Annalen,  vol.  237,  p.  327)  reserves  the  name  of  quinoxalines  to 
compounds  which  contain  the  nucleus: 


at  the  end  of  a  chain  of  hexagonal  nuclei,  ancl  gives  the  name  of  azines  to  those 
•which  contain  the  same  nucleus  in  the  midle  of  such  a  chain: 


Quinoxaline.  Azine  (diphenazine). 

*  For  the  condensation  of  amines  with  carbohydrates,  see  W.  Sorokine,  Action 
of  Qlucose  on  Aniline  and  Toluidine,  Kasan,  1887  (in  Russian). 


174  ORGANIC  SYNTHESES. 

ester  with  urea)  and  concentrated  sulphuric  acid,  uric  acid  is 
produced  :  l 

C4H4N204  +  CO.N2H4  =  CsILJ^Oa  +  2H20. 

The  formation  of  uric  acid  under  these  conditions  leads  to  the 
following  formula  for  this  body  : 

NH-C.HNX 
I         II        >0. 
CO     C.HN/ 

NH—  CO 

(c)  Ammonia  Derivatives  formed  with  Liberation  of  H2S,  — 

Bodies  containing  the  CS  group  react  with  amines  in  the  same 
manner  as  bodies  containing  CO.  Thus,  diphenyl-thio-urea  in 
alcoholic  solution  condenses  with  aniline  in  the  presence  of  a 
metallic  oxide  to  yield  triphenyl-guanidine  : 


<\TTT 
N? 


Carbon  disulphide  with  aromatic  amines  gives  substituted 
derivatives  of  thio-urea  with  liberation  of  hydrogen  sulphide. 
Thus  aniline  heated  with  carbon  disulphide  and  alcohol  (with 
an  inverted  condenser)  gives 


C\NH.C6H5' 

For  the  action  of  carbon  disulphide  on  the  aliphatic  amines, 
see  under  removal  of  hydrogen  sulphide. 

1  See  Annalen,  vol.  251,  p.  235. 


CONDENSATIONS.  175 

(d)  Ammonia  Derivatives  formed  with  Liberation  of  NH3.— 
The  primary  amines,  on  heating,  are  frequently  converted 
into  secondary  amines: 

R.NH2 + R.NH2 = R2.NH + NH3. 

This  reaction  is  facilitated  by  adding  some  substance  capable 
of  absorbing  ammonia,  such  as  calcium  chloride  or  zinc  chloride,, 
or  acids. 

Dianthramine  is  readily  formed  by  heating  anthraminer 
Ci4H9.NH2,  with  boiling  glacial  acetic  acid;  as  a  secondary 
product  there  is  formed  aceto-anthramine : 

C14H9.NH.CO.CH3. 

The  best  method  of  obtaining  certain  secondary  amines  is 
to  heat  the  amine  with  its  hydrochloride : 

C6H5.NH2 + C6H5.NH2.HC1  =  (C6H5)  2NH + NH4C1. 

In  this  manner  secondary  amines  may  be  obtained  with  different 
radicals,  and  also  secondary  acid  amides.  The  reaction  between 
an  amine  and  an  acid  amide  takes  place  readily.  If  acetamide 
is  heated  with  aniline  until  ammonia  is  no  longer  disengaged, 
acetanilide  is  obtained  in  theoretical  amount.  Urea  behaves 
in  the  same  manner;  heated  with  aniline  or  its  hydrochloride, 
it  gives  phenyl-urea: 


fused  with  an   excess  of  meta-amido-benzoic  acid,  it   gives 
uramido-benzoic  acid: 

FH2 

LC6H4.CO.OH. 


1  76  ORGANIC  SYNTHESES. 

With  an  excess  of  amine,  urea  gives  disubstituted  ureas.  In 
some  cases  the  NH  group  of  amidines  react  with  amines;  for 
example  : 


(2)  DERIVATIVES  OF   THE    DIAMINES  R(NH2)2  AND   THE 
DIIMIDES  R(NH)2. 

(a)  Substituted  Hydrazines.  —  The  hydrazine  substitution 
products  (symmetrical)  are  obtained  from  phenylhydrazine  by 
the  action  of  bromine  compounds,  acid  chlorides,  acid  anhy- 
drides, and  acid  amides. 

Phenylhydrazine  condenses  with  aldehydes  and  ketones 
with  liberation  of  water,  this  being  a  characteristic  reaction 
for  this  body.  With  benzaldehyde,  for  example,  it  gives 
C6H5.CHiN.NH.C6H5.1  The  unsaturated  aldehydes  and  ke- 
tones give  hydrazine  derivatives,  which  on  distillation  lose 
H2  and  are  converted  into  pyrazol  derivatives.  Thus,  the 
product  of  the  reaction  of  acrolein  on  phenylhydrazine  gives 
phenylpyrazol  : 

N  =  CH.CH=CH2  N=CH.CH 

NH.C6H5 


1  Glucose,  like  the  aldehydes,  reacts  in  the  cold  with  one  molecule  of  phenyl- 
hydrazine with  liberation  of  water.  On  heating  with  phenylhydrazine,  two 
molecules  enter  into  reaction,  and  a  yellow  precipitate  is  formed.  The  reaction 
may  be  represented  by  the  equation: 

C6H1206+  2NH2.NH.C6H5=  C6H10O4(N.NH.C6H5)2+  2H2O+  H2. 

It  is  interesting  to  know  that,  through  this  compound,  dextrose  may  be  con- 
verted into  laevulose;  on  reduction  of  the  hydrazine  derivative,  there  is  formed 
iso-glucosamine,  C6Hn(NH2)O5,  and  this,  by  treatment  with  nitrous  acid,  ia 
completely  converted  into  laevulose. 


CON  DENS  A  TIONS.  1 7  7 

Among  the  derivatives  of  pyrazol  is  found  antipyrine   (used 
as   a   febrifuge   and    analgesic),    which    is    obtained    by   the 
condensation  of  ace  to-acetic  ester  with  methyl-phenyl-hydra- 
zine    (symmetrical)    with    liberation    of   water   and    alcohol 
C2H5.OH. 

For  derivatives  of  phenylhydrazine,  see  page  179. 

(b)  Diazo-amido  Compounds. — On  mixing  the  aqueous  or 
alcoholic  solutions  of  a  diazo-salt  and  an  amido  compound, 
there  is  formed  a  diazo-amido  body: 


N.C6H5  N.C6H5 

1 1  +2C6H5.NH2  =  1 1  +C6H5.NH2.HN03. 

N.O.N02  N.NH.C6H5 


If  the  diazo-salt  and  the  primary  amine  contain  different 
radicals,  there  are  formed  diazo-amides  which  are  identical 
whether  R.N:N.C1  reacts  on  R'NH2  or  R'N:N.C1  on  R.NH2. 
But  in  the  case  of  secondary  amines,  under  the  same  condi- 
tions, there  will  be  formed  two  different  isomers.  Thus,  by  the 
action  of  diazobenzene  chloride,  CeHs.NrN.Cl,  on  mono-ethyl- 
toluidine,  C6H4(CH3)NH.C2H5,  a  body  is  formed  which  shows 
different  properties  and  decomposition  products  from  that 
formed  by  the  action  of  diazo-toluene  chloride,  C6H4.(CH3)N: 
N.C1,  on  ethyl-aniline,  C6H5.NH.C2H5. 

The  formation  of  diazo-amido  derivatives  by  the  action  of 
nitrous  acid  on  amido  compounds  and  their  salts  must  be 
regarded  as  the  result  of  two  successive  reactions:  firstly,  the 
formation  of  a  diazo-body,  like  C6H5.N  :N.OH  or  its  salt;  and, 
secondly,  the  action  of  this  body  on  the  amine  with  liberation 
of  water. 

Thus,  the  diazo-amido  compounds  are  obtained  with  the 
chlorides  of  the  diazo  compounds  by  the  action  of  NaN02  on 
R.NH2.HC1  in  neutral  solution;  but  in  an  alkaline  solution 
there  is  formed  only  the  diazo-amido  compound.  For  example, 


I  78  ORGANIC  SYNTHESES 

N.C6H5 

2C6H5.NH2.HC1 + NaN02  +  NaOH  =  1 1  +  2NaCl + 3H20 

N.NH.C6H5 


The  diazo-amido  compounds  are  also  obtained  by  the  actioa 
of  N203  on  a  cooled  alcoholic  solution  of  the  amine;  the  diazo- 
amido  body,  being  but  slightly  soluble,  immediately  separates 
out.  The  ethereal  solution  of  the  amine  may  also  be  treated 
with  a  nitrous  ester. 

In  the  preparation  of  the  diazo-amido  bodies,  it  is  necessary 
to  take  into  consideration  the  ease  with  which  they  pass  into- 
the  isomeric  amido-azo  compounds. 

(c)  Azo  Derivatives.  —  In  certain  cases,  in  the  reaction  of  diazo- 
salts  on  amido  compounds,  in  place  of  diazo-amido  bodies^ 
there  are  directly  obtained  their  isomers,  the  amido-azo  com- 
pounds.1 

If  meta-phenylene-diamine,  C6H4<^  Lc  NTT2'    *S 


diazo-benzene  nitrate,  CeHs.N  :  N.ON02  (action  of  nitrous  acid 
on  aniline  nitrate,  C6H5.NH2.HN03),  there  is  formed  chrysoidine 
nitrate  : 

N.C6H5 

II 
N.C6H3(NH2)2HN03. 

It  is  not  necessary,  in  the  preparation  of  these  bodies,  to- 
separate  the  diazo-salts;  they  may  be  obtained  by  the  action 
of  nitrous  acid  on  a  mixture  of  the  amines.  Thus,  if  a  cooled 
alkaline  solution  of  sodium  nitrite  is  gradually  added  to  a  mix- 
ture of  the  hydrochlorides  of  aniline  and  dimethylaniline,  there 
is  formed: 

C6H5.N:N.C6H4.N(CH3)2. 

1  For  the  formation  of  the  azo  derivatives  by  direct  addition,  see  p.  155. 


CON  DENS  A  TIONS.  179 

In  the  same  manner,  by  the  action  of  nitrous  acid  on  meta- 
phenylene-diamine,  triamido-azo-benzene  is  formed  : 

NH2.C6H4.N:N.C6H3(NH2)2. 

It  is  probable  that  there  is  at  first  formed  NH2.C6H4.N:N.OH, 
which  then  reacts  on  another  molecule  of  C6H4(NH2)2. 

The  salts  of  the  diazo  compounds  react  readily  with  phenols 
and  their  derivatives: 

C6H5.N  :N.N03 + C6H5.OH  =  C6H5.N  :N.C6H4.OH  +  HN03. 

To  prepare  hydroxy-azobenzene,  a  solution  of  30  gms.  of 
potassium  nitrite  in  4  litres  of  water  is  added  to  a  solution  of 
20  gms.  of  phenol  in  2  litres  of  water.  On  agitating,  there  is 
at  first  formed  a  yellow  precipitate  which  becomes  red.  After 
standing  for  21  hours,  the  precipitate  is  dissolved  in  ammonia 
in  order  to  separate  it  from  resinous  matters.  The  solution  is 
reprecipitated  by  the  addition  of  acid,  and  the  compound  is 
finally  crystallized  from  boiling  dilute  alcohol. 

In  the  reactions  of  diazo-salts  on  phenols  and  amines,  the 
N:N  group  takes  the  para-position  generally  with  respect  to 
the  OH  or  NH2  group,  and  the  ortho-position  when  the  para 
is  occupied. 

The  salts  of  the  diazo  compounds  condense  also  with  metal- 
lic derivatives,  with  nitro  compounds  of  the  aliphatic  series, 
with  esters,  and  with  ke  tonic  acids  like  ace  to-acetic  acid;  but 
in  such  cases  azo  derivatives  are  not  obtained,  but  derivatives 
of  phenyl  hydrazine.  Thus,  with  ace  to-acetic  ester,  there  is 

H    CO.CH3 

formed  the  ester  of  a  rather  stable  acid,  , 

C6H5N:N  =  C.CO.OC2H5 

which  only  decomposes  at  180°  C.,  giving  carbonic  acid  and 
CH3.CO.CH:N.NH.C6H5. 

The  azo  compounds  are  obtained'  by  the  oxidation  of  aro- 
matic amido  compounds,  4H  being  removed  from  two  molecules 


i8o  ORGANIC  SYNTHESES. 

of   the  amine.    Thus,  aniline,  oxidized  with  potassium  per- 
manganate, gives  azo-benzene: 


C6H5.N 
C6H5.N 


-2H2  = 


C6H5.N 

II 
C6H5.N 


Other  oxidizing  agents  may  also  be  employed,  such  as  potas- 
sium ferricyanide  in  alkalines  olution,  chromic  acid  in  acetic 
acid  solution,  hydrogen  peroxide,1  or  even  by  passing  the 
vapors  of  the  amine  over  heated  lead  oxide. 

The  oxidation  of  the  disubstituted  hydrazines  may  be 
carried  out  by  agitating  their  aqueous  or  alcoholic  solution 
with  the  oxide  of  mercury  or  silver,  Hg20,  or  Ag20,  or  by 
employing  ferric  chloride.  The  disubstituted  hydrazines  are 
easily  decomposed: 


NH     +  02  =   65N-N  :  N.N  +  2H20. 


(d)  Azoxy  Compounds.  —  The  aromatic  nitro  compounds,  by 
the  action  of  alkaline  reducing  agents,  are  converted  into  azoxy 
compounds  by  the  removal  of  three  molecules  of  oxygen  from 
two  molecules  of  the  nitro-body: 

R.Nv 

2R.N02  +  3H2=      |   >0+3H20. 
R.N/ 

The  nitro-body  is  treated  with  an  alcoholic  solution  of 
caustic  potash  (Zinin's  process).  In  some  cases,  for  example 
with  azoxy-benzene,  a  better  result  is  obtained  by  using  sodium 
methylate  dissolved  in  methyl  alcohol.  To  prepare  the  azoxy 
bodies,  it  is  convenient  to  employ  sodium  amalgam,  which  is 

1  Barzilovsky,  On  the  Azo  Derivatives  of  Toluene,  Kieff,  1878  (in  Russian). 


CONDENSATIONS.  181 

allowed  to  act  on  the  aqueous  or  alcoholic  solution  of  the  nitro- 
compound.  To  avoid  the  formation  of  an  azo-body,  produced 
by  the  oxidation  of  the  hydrazo  compound  which  is  at  first 
formed,  the  sodium  amalgam  is  added,  a  little  at  a  time,  and 
in  slight  excess  only,  at  a  temperature  as  low  as  possible.  There 
is  always  formed  a  small  quantity  of  azo  derivative,  which  is 
removed  by  treating  the  product  with  tin  chloride,  SnCl2,  and 
sulphuric  acid.  Zinc  dust,  caustic  potash,  and  stannous  oxide 
in  alkaline  solution,  are  all  good  reducing  agents,  but  they 
react  too  energetically;  they  are  only  employed  for  the  prepara- 
tion of  hydrazo  or  azo  bodies. 


CHAPTER  VIII. 

TYPES   OF  SYNTHESES. 

I.  FIXATION  OF  CARBON  MONOXIDE  (CO). 

CARBON  monoxide  combines  with  alkalies,  and  gives  salts 
of  formic  acid;  it  also  combines  with  alcoholates  to  give  salts 
of  the  homologues  of  formic  acid: 

CH3.CH2.ONa  +  CO  =  CH3.CH2.CO.ONa. 

If,  instead  of  an  alcoholate,  there  is  taken  its  mixture  with  a 
salt  of  an  acid,  there  are  obtained  acids  having  an  increased 
number  of  carbon  atoms. 

Carbon  monoxide,  at  the  moment  of  its  formation,  combines 
with  phenols  and  their  derivatives,  the  hydrogen  of  the  CH 
group  passing  into  the  CHO  group.  Phenol,  in  this  manner, 
is  converted  into  salicyl  aldehyde  by  the  simultaneous  action 
of  caustic  soda  and  chloroform  : 


In  carrying  out  this  reaction,  two  to  three  times  the  theo- 
retical amounts  of  chloroform  and  caustic  soda  are  taken;  the 
chloroforfn  is  added  drop  by  drop  to  the  alkaline  solution  of 
the  phenol  slightly  heated;  by  raising  the  temperature  the 
reaction  is  finally  completed.  The  liquid  is  then  acidulated; 
the  excess  of  phenol  is  distilled  off  in  a  current  of  steam;  then 
the  liquid  is  filtered  to  remove  resinous  matters,  and  the  alde- 

hyde which  has  been  formed  is  extracted  with  ether.    If  it 

182 


TYPES  OF  SYNTHESES.  183 

distils  with  steam,  it  is  separated  from  the  phenol  by  means 
of  sodium  bisulphite,  NaHSOs.  Distillation  in  steam  can  also 
be  used  in  order  to  separate  the  isomers  which  may  be  formed; 
ortho-oxy-aldehydes  are  generally  much  more  volatile  than 
para-isomers. 

The  reaction  of  phenols  with  caustic  soda  and  chloroform 
can  be  considered  as  a  condensation,  with  liberation  of  water, 
of  the  phenol  with  the  tri-hydrate  which  is  at  first  formed: 

CHC13  +  3NaOH  =  CH  (OH)  3  +  3NaCl, 


+  H20. 


The  formation  of  ketones  affords  a  special  case  of  the  fixa- 
tion of  carbon  monoxide;  for  example,  the  formation  of  ethyl- 
ketone,  C2H5.CO.C2H5,  by  the  action  of  carbon  monoxide  on 
sodium  ethyl,  C2H5.Na.  Carbon  monoxide,  when  heated  with 
potassium,  gives  K6C606,  a  potassium  salt  of  hexa-oxybenzene; 
the  same  product  is  also  obtained  as  a  secondary  product  in 
the  preparation  of  potassium.  With  alcohol  this  compound 
gives  the  salt  of  rhodizonic  acid,  C6(02)(02)(OK)2. 

II.  FIXATION  OF  CARBON  DIOXIDE  (C02). 

The  fixation  of  carbon  dioxide  by  hydrocarbons  (for  instance, 
benzene)  only  takes  place  in  the  presence  of  aluminium  chloride  : 

C6H6+C02=C6H5.CO.OH.  * 

With  sodium  compounds,  however,  the  reaction  takes  place 
more  easily.  Thus,  CH3.CH2Na  gives  the  sodium  salt  of  pro- 
pionic  acid;  NaC=C.C6H5is  converted  into  the  salt  of  phenyl- 
propiolic  acid. 


1 84  ORGANIC  SYNTHESES. 

The  formation  of  benzoates  by  the  action  of  carbon  dioxide 
and  sodium  on  brom-benzene,  C6H5Br,  is  really  the  fixation 
of  C02  by  C6H5Na  at  the  moment  of  its  formation. 

Sodium  acetanilide  combines  with  carbonic  acid  in  the  cold: 


The  product  which  is  formed  gives  an  isomer  when  heated,  the 
anilide  of  malonic  acid  being  formed : 

C6H5  N/CO.CH2.CO.ONa 
\H 

The  phenates  combine  with  carbonic  acid  on  heating,  and 
are  converted  into  oxy-acids;  phenol  gives  salicylic  acid.  There 
is  at  first  formed  the  salt  of  the  acid  ester  of  carbonic  acid: 

'ONa 
>.C6H5> 

which  afterwards,  on  heating  to  120-130°  C.,  becomes  isom- 
erized  into  sodium  salicylate : 

m/ONa        p  H  /OH 
\O.C6H5=C6H4\CO.ONa' 

The  most  convenient  method  of  preparing  salicylic  acid  is  to 
add  liquid  carbonic  acid  to  the  absolutely  dry  phenate  enclosed 
in  an  autoclave;  the  mixture  is  heated  for  several  hours  at 
120-130°  C. 

By  heating  sodium  salicylate  in  a  current  of  carbon  dioxide 
to  200°  C.,  there  are  formed  the  salts  of  dicarboxyl  and  tricar- 
boxylphenol  acids,  C6H3.OH(CO.OH)2  and  C6H2.OH(CO.OH)3. 
Polyhydric  phenols  will  also  combine  with  carbon  dioxide  when 
heated  with  an  aqueous  solution  of  ammonium  carbonate. 


TYPES  OF  SYNTHESES.  185 

The  sodium  compound  of  oxy-quinoline,  heated  with  liquid 
carbon  dioxide,  is  converted  entirely  into  oxy-quinoline  car- 
boxylic  acid: 

C9H6(ONa)N  +  C02=C9H5(OH)(CO.ONa)N. 

The  formation  of  oxy-acids  by  treating  phenols  with  carbon 
tetrachloride,  CCU,  and  caustic  soda,  can  be  considered  as  the 
fixation  of  carbon  dioxide  in  the  nascent  state,  or  as  a  con- 
densation of  the  tetrahydrate  of  carbon  and  phenol  with  loss 
of  water  : 


C(OH)3+H2°> 
NCOH3  =  C6H4co  OH+H20. 


The  reaction  is  brought  about  by  adding  carbon  tetrachloride 
and  alcohol  to  a  strongly  alkaline  solution  of  phenol  until 
completely  dissolved;  the  mixture  is  then  heated  in  a  sealed 
tube  until  sodium  chloride  is  no  longer  formed. 

The  fixation  of  carbon  dioxide  can  be  brought  about  by 
the  substitution  of  H  by  CN,  which  is  then  saponified;  or  the 
S02.OH  group  may  be  replaced  by  CO.OH. 

III.  CONDENSATION  BY  THE  TRANSFORMATION  OF  THE 
CO  GROUP  INTO  C.OH  AND  C.OX. 

In  the  reduction  of  aldehydes  and  ketones,  two  molecules 
combine  with  the  addition  of  hydrogen  to  form  dihydric  alco- 
hols; and  the  CO  group  is  converted  into  C.OH.  Benzalde- 
hyde  behaves  in  this  manner;  with  zinc  and  hydrochloric  acid 
in  alcoholic  solution  it  gives  hydrobenzoin  : 

C6H5.CH.OH 
2C6H5.COH+H2=  | 

C6H5.CH.OH 


ORGANIC  SYNTHESES. 

The  sodium  derivative  of  this  glycol  can  be  obtained  by  the 
action  of  sodium  amalgam  on  benzaldehyde  in  the  absence  of 
water. 

Some  aldehydes  of  the  aliphatic  series  are  converted  into 
dihydric  alcohols  by  the  use  of  alcoholic  soda.  Thus,  isobutyric 
aldehyde,  (CH3)2.CH.CHO,  gives  a  glycol  simultaneously  with 
isobutyric  acid: 

(CH3)2.CH.CH.OH 

(CH3)2.CH.CH.OH 

The  reaction  may  also  be  carried  out  by  the  condensation 
of  two  different  aldehydes.  Thus,  a  mixture  of  ordinary  alde- 
hyde and  isobutyric  aldehyde  with  sodium  amalgam  will  give  : 

(CH3)2.CH.CH.OH 
CH3.CH.OH' 

For  the  formation  of  the  compound,  [(C6H5)2CSH]2,  see 
under  substitutions. 

The  reduction  of  the  CO  group  to  C.OH  does  not  take  place 
by  the  action  of  free  hydrogen,  but  by  the  hydrogen  of  another 
molecule  of  the  same  substance.  The  formation  of  aldol 
according  to  Wurtz,  by  the  action  of  hydrochloric  acid  on 
aldehyde,  is  a  reaction  of  this  kind: 

CH3.CHO  +  CH3.CHO  =  CH3.CH(OH).CH2.CHO. 

Aldol. 

The  formation  of  aldol  may  be  considered  as  a  condensation 
of  a  dihydrate  with  aldehyde  and  liberation  of  water,  or  as  a 
condensation  of  chlorhydrin,  CH3CH(OH)C1,  with  aldehyde  and 
liberation  of  hydrochloric  acid  : 


4-  HCH2.CHO  =  CH3.CH(OH)  .CH2.CHO  +  H20. 
CH3.CH(OH)C1  +  HCH2.CHO  =  CH3.CH(OH)  .CH2.CHO  +  HC1. 


TYPES  OF  SYNTHESES.  187 

A  1  per  cent,  solution  of  caustic  soda  on  a  solution  of  ortho- 
nitrobenzaldehyde  in  acetone,  gives  rise  to  a  reaction  which 
may  be  expressed  as  follows  : 


_rH/(l)N02 
U±l4\(2)  CH(OH).CH2.CO.CH3. 

In  the  aromatic  series  the  condensation  of  aldehydes  takes- 
place  a  little  differently;  that  is  to  say,  the  CO  group  of  the 
aldehyde  radical  is  converted  into  C.OH  at  the  expense  of  the 
hydrogen  of  the  other  CHO  group.  It  is  in  this  manner  that 
benzaldehyde  is  converted  into  benzoin  by  the  action  of  a 
dilute  alcoholic  solution  of  potassium  cyanide  : 

C6H5.CO 
C6H5.CHO+C6H5.CHO  =  | 

C6H5.CH.OH 

The  conversion  of  the  CO  group  into  C.OH  is  also  brought 
about  by  the  union  of  hydrocyanic  acid  with  aldehydes  and 
ke  tones  : 

CH3.CHO  +  HCN  = 

This  reaction  is  carried  out  by  leaving  the  aldehyde  in  contact 
with  the  theoretical  quantity  of  hydrocyanic  acid  (25  per  cent. 
aqueous  solution)  at  the  ordinary  temperature,  or  by  slightly 
heating.  The  acid  reacts  more  readily  in  the  nascent  condition; 
to  obtain  this  condition,  the  aldehyde  or  ketone  in  ethereal  solu- 
tion is  mixed  with  the  theoretical  quantity  of  moist  potassium 
cyanide,  after  which  there  is  added  drop  by  drop  the  calculated 
amount  of  a  concentrated  mineral  acid. 

In  certain  cases,  the  cyanhydrins  of  dihydrates  1  which  are 

1  The  anhydrides  of  the  glycols  also  combine  with  hydrocyanic  acid  to  form 
cyanhydrins.     Through   the  intervention   of  the  cyanhydrins  it  is  possible  to> 

<OTT 
CO  OH* 


1 88  ORGANIC  SYNTHESLS. 

formed  (as,  for  example,  acetone  cyanhydrin)  readily  condense 
with  splitting-off  of  hydrocyanic  acid: 


(CH3)2.C.OH 


(CH3)2.C.CN 

A  series  of  synthetic  methods  is  based  on  the  transformation 
of  the  CO  group  into  C.OX,  brought  about  by  the  action  of 
metallo-organic  compounds  on  aldehydes,  ketones,  etc.  The 
aldehydes  at  first  give  condensation  products  : 


\OZnR'1 

which  subsequently,  on  decomposition  with  water,  replace  the 
OZnR'  group  with  OH  and  form  secondary  alcohols : 


Formaldehyde,  with  organic  compounds  of  zinc,  gives  primary 
alcohols. 

The  reaction  takes  place  well  only  with  zinc-ethyl  or  zinc- 
methyl;  with  the  higher  homologues,  ZnR2,  there  occurs  at  the 
same  time  a  reduction  of  the  aldehyde  to  the  corresponding 
alcohol. 

The  halogen  substituted  compounds  of  the  aldehydes  only 
react  well  with  zinc-ethyl;  with  the  homologues  of  the  latter, 
there  is  simply  a  reduction  of  the  aldehyde. 

The  general  method  of  obtaining  secondary  alcohols  (Wag- 
ner's method)  is  by  the  action  of  water  on  the  condensation 
products  of  aldehydes  with  organo-metallic  compounds. 


TYPES  OF  SYNTHESES.  189 

The  action  of  formic  and  acetic  esters  on  organo-metallic 
compounds  can  be  considered  in  two  phases:  there  is  at  first 
formed  aldehyde,  which  then  reacts  with  another  molecule  of 
the  organo-metallic  compound.  Thus,  the  preparation  of  iso- 
propyl  alcohol,  according  to  the  general  method  of  Zaytzeff  for 
the  making  of  secondary  alcohols,  can  be  expressed  by  the  fol- 
lowing equations,  which  represent  the  action  of  ethyl  formate 
on  zinc-methyl  : 

CHO      CH3 

|         +  |  =  CH3.CHO+CH3.OZn.CH3. 

OCH3    Zn.CH3 

CH3.CHO  + 


The  ketones  behave  in  exactly  the  same  manner  as  alde- 
hydes, not  only  with  organo-metallic  compounds,  but  also  with 
Zn  and  RI  ;  condensation  products  are  obtained  which  are 
decomposed  with  water  with  formation  of  tertiary  alcohols. 
This  is  a  general  method  applied  by  Zaytzeff  for  the  prepara- 
tion of  unsaturated  tertiary  alcohols.1  Thus  acetone,  by  treat- 
ment with  zinc  and  allyl  iodide,  followed  by  water,  gives  allyl- 
dimethyl-carbinol  : 


(CH»)  2CO  +  C3H5I  +  Zn  =  (CH3)  ^\QZiil ' 

'OH 


(CH8)  2C<  +  H20  =  (CH8) 


The  preparation  of  tertiary  alcohols  by  ButlerofFs  method 
(action  of  organo-metallic  compounds  on  acid  chlorides)  can 
be  considered  as  the  result  of  a  reaction  between  the  organo- 

1  With  the  exception  of  ketones  containing  the  CH3  group,  as  these  form 
condensation  products. 


Jpo  ORGANIC  SYNTHESES. 

metallic  compound  and  a  ketone  at  first  formed;  but  it  is  more 
probable  that  it  is  simply  a  replacement  of  chlorine  by  R  in 
the  condensation  product  formed  in  the  first  place  :  l 

/Cl 

R.CO.C1  4-  ZnR'2  =  R.Cf-OZnR'. 
\R' 

To  prepare  the  tertiary  alcohols  by  allowing  R.CO.C1  to  act 
on  ZnR'2,  it  is  necessary  to  cool  the  compound  which  is  at  first 
formed  before  decomposing  it  with  water;  otherwise  but  a  very 
small  yield  of  alcohol  will  be  obtained.  The  reaction  with  ZnR2 
proceeds  slowly,  and,  if  the  product  of  the  reaction  is  immediately 
decomposed  with  water,  only  a  ketone  will  be  obtained. 

With    zinc-propyl    and    acetyl-chloride,    CH3.CO.C1,    the 

/C3H7 
product  which  is  formed,  CH3.C£-OZnC3H7,  is  decomposed  by 

\C1 

water  with  the  formation  of  a  secondary  alcohol.  The  prepara- 
tion of  oxy-carboxylic  acids,  by  the  action  of  RI  and  zinc  on 
oxalic  ester,  can  be  considered  as  a  transformation  of  the  CO 
group.  For  example,  the  preparation  of  dime  thy  1-gly  oxalic 
acid  may  be  represented  as  follows: 


IZnO      CH3 


CO.OC2H5  C.OC2H5       CO.CH3 

+  CH3I  +  Zn=  |  p  TT 

CO.OC2H5  CO.OC2H5    CO.OC2H5 

CO.CH3  /CH3 

|  +CH3I  +  Zn  =  C^-CH3  . 

CO.OC2H5  |  \OZnI 

CO.OC2H5 

The  zinc  derivative,  by  the  action  of  water,  splits  off  OZnl  for 
OH. 

1  P.  Menchtchikoff,  On  the  Reaction  of  Zinc  Ethyl  on  Butyrone,  Kazan,  1887 
(in  Russian). 


TYPES  OF  S YNTHESES.  1 9 1 


IV.  CONDENSATION   WITH  LOSS  OF  WATER. 

It  is  probable  that,  in  the  majority  of  cases,  the  liberation  of 
water  is  only  a  second  phase  of  condensations,  and  the  compound 
at  first  formed  is  after  the  type  of  an  aldol.  In  fact,  if  ordinary 
aldehyde  is  heated  to  100°  C.  with  dehydrating  agents,  such 
as  a  concentrated  solution  of  sodium  acetate,  the  aldol,  which 
is  at  first  formed  by  the  loss  of  water,  is  converted  into  crotonic 
aldehyde,  CH3.CH:CH.CHO.  (Enanthol  behaves  in  the  same 
manner  on  treatment  with  alcoholic  potash  or  a  small  quantity 
of  zinc  chloride. 

Acetic  acid  condenses  with  benzaldehyde  to  give  cinnamic 
acid,  CeHs.CHiCH.CO.OH;  it  may  be  assumed  that  this  acid 
is  derived  from  phenyl-lactic  acid,  C6H5.CH2.CH(OH).CO.OHr 
otherwise  known  as  tropic  acid.1 

In  certain  cases,  the  condensation  takes  place  readily,  even 
without  dehydrating  agents.  Thus,  chlor-aldehyde,  heated 
alone,  condenses  to  a-^-dichlor-cro tonic  aldehyde : 

2(CH2C1.CHO)=CH2C1.CH:CC1.CHO  +  H20. 

Two  different  aldehydes  can  condense  in  the  same  manner. 
With  ordinary  aldehyde  and  benzaldehyde,  there  is  formed  the 
aldehyde,  C6H5.CH:CH.CHO.  This  reaction  is  carried  out  by 
saturating  the  mixed  aldehydes  with  hydrochloric  acid  gas  and 
heating,  or  even  by  leaving  the  mixed  aldehydes  for  8  to  10 
hours  at  30°  C.  with  a  dilute  solution  of  caustic  soda. 

It  is  probable  that  in  these  condensations  the  CO  group  of 
one  molecule  always  reacts  with  that  carbon  group  attached 
to  the  CO  group  in  the  other  molecule. 

1  With  Perkin's  reaction  it  is  possible  to  prepare  an  acetyl  derivative  of  phenyl- 
acetic  acid,  C6H5.CH(C2H3O)CH2.COOH;  but  this  compound  decomposes  at 
the  temperature  at  which  the  reaction  takes  place  into  acetic  and  cinnamic  acids. 
An  acetyl  derivative  is  apparently  obtained  by  heating  benzaldehyde  with  an 
iso-butyrate  and  acetic  anhydride.  This  compound,  C6H5.CH(C2H3O).(CH3)2. 
COOH  is  not  decomposed  with  the  formation  of  acetic  acid. 


*92  ORGANIC  SYNTHESES. 

Ketones  condense  in  the  same  manner  as  aldehydes.  Ace- 
tone gives  mesityl  oxide,  phorone,  and  mesitylene.  There  is 
.also  formed  between  the  acetone  and  mesityl  oxide  an  inter- 
mediate compound  analogous  to  aldol:  (CH3)2.C(OH).CH2.CO. 
€H3.  This,  with  concentrated  sulphuric  acid,  is  decomposed 
into  water  and  mesityl  oxide:  (CH3)2C:CH.CO.CH3. 

In  condensations  between  ketones  and  aldehydes  (but  only 
those  of  the  aromatic  series),  the  oxygen  of  the  aldehyde  is 
eliminated  in  the  form  of  water.  Acetone  and  benzaldehyde, 
for  instance,  give  benzylidene  acetone;  then  another  molecule 
of  aldehyde  reacts  to  form  dibenzylidene  acetone  : 


:  CH 

C6H5.CH  : 


The  ketophenone,  containing  but  one  CH3  group,  only 
reacts  with  one  moleculee  of  benzaldehyde  to  form  C6H5.CH  : 
€H.CO.C6H5.  The  condensation  takes  place  in  a  closed  vessel; 
the  mixture,  well  cooled  and  saturated  with  hydrochloric  acid 
gas  (or  the  alcoholic  or  aqueous  solution  of  the  substances  to 
be  condensed,  with  the  addition  of  a  little  caustic  soda),  is 
allowed  to  stand  for  some  days;  it  is  then  extracted  with  ether. 

The  synthesis  of  unsaturated  acids  is  carried  out  by  the 
reaction  of  Bertagnini  and  by  that  of  Perkin,  which  is  a  modi- 
fication of  the  former.  Bertagnini  has  succeeded  in  synthesizing 
cinnamic  (phenyl-acrylic)  acid  by  heating  benzaldehyde  with 
acetyl  chloride  : 

C6H5.CHO  +  CH3.CO.C1  =  C6H5CH  :  CH.CO.OH  +  HC1. 

Perkin  has  effected  the  same  synthesis  by  an  analogous  proce- 
dure, which  he  has  applied  to  the  preparation  of  a  number  of 
unsaturated  acids.  He  allows  the  aldehyde  to  react  on  the 
acid  in  the  presence  of  dehydrating  agents,  taking  generally  the 
sodium  salt  of  the  acid  and  using  acetic  anhydride  as  the  con- 
densing agent,  or,  which  is  better  still,  the  anhydride  of  the 


T  YPES  OF  S  YN THESES.  1 93 

acid  used.  This  reaction  takes  place  with  aldehydes  of  both  the 
aliphatic  and  aromatic  serfes  and  their  derivatives.  Thus, 
cuminic  aldehyde,  with  sodium  acetate,  gives  cummyl-acrylic 
acid: 

CH.(CH3)2 
CHiCH.CO.OH' 

The  phenol  aldehydes,  like  salicyl-aldehyde,  give  unsaturated 
oxy-acids  or  their  lactones.  Thus,  salicyl-aldehyde  with  acetic 
acid  gives  coumarin,  the  lac  tone  of  coumaric  acid.  In  this 
reaction,  according  to  Grimaux,  there  is  formed  an  intermediate 
body  of  the  aldol  type,  which  loses  the  elements  of  water  at 
the  moment  of  its  formation : 

/CHO    CH3  /CH.(OH> 


/  3  /.v 

Cell/         +|  =C6H4<  >CH2+H20; 

XOH      CO.OH  X)  --  CO/ 

Intermediate  body. 

CeH^  Q  _  QQ  /CH2  —  H20  =  CeH^  Q  QQ  "^CH. 


Coumarin. 

This  reaction  is  carried  out  by  heating  1  part  aldehyde,  1 
part  dehydrated  sodium  acetate,  and  1J  parts  acetic  anhydride 
for  8  to  12  hours  on  an  oil-bath  at  150-160°  C.,  using  an  inverted 
condenser.  The  product  of  the  reaction  is  dissolved  in  a  dilute 
alkaline  solution;  the  unattacked  aldehyde  is  removed  by 
ether.  The  coumarin  is  precipitated  from  its  alkaline  solution 
by  addition  of  hydrochloric  acid,  and  is  crystallized  from  benzene. 

Aldehydes  and  ketones  also  condense  with  dicarboxylic 
acids.  Thus: 

CH3.CHO+CH2.(CO.OH)2-H20  =  CH3.CH:C.(CO.OH)2. 

Ethylidene  malonic  acid. 

The  reaction  is  carried  out  by  saturating  the  cooled  mixture  of 
aldehyde  and  acid  with  hydrochloric  acid  gas,  or  by  heating  the 
mixture  in  a  sealed  tube  with  acetic  anhydride  or  glacial  acetic 
acid.  Secondary  products  are  obtained;  in  the  above  example, 


194  ORGANIC  SYNTHESES. 

for  instance,  some  crotonic  acid  is  formed  by  reason  of  the 
splitting-off  of  carbon  dioxide. 

Succinic  acid,  in  condensing,  also  gives  rise  to  intermediate 
compounds  of  the  aldol  type,  but  only  in  the  form  of  the  sodium 
salt.  With  benzaldehyde,  the  salt  of  the  following  oxy-acid  is 
formed : 

C6H5.CH(OH)  .CH.CO.OH 
CH2.CO.OH* 

This  acid,  on  treatment  with  acetic  acid,  immediately  decom- 
poses with  the  formation  of  a  lactone : 

CO.OH 
C6H5.CH.CH.CH2.CO. 

!_ o— I 

The  anhydrides  of  the  dicarboxylic  acids  (for  example r 
phthalic  anhydride)  behave  in  the  same  manner  as  aldehydes. 
Heated  with  sodium  acetate  and  acetic  anhydride,  it  gives 
phthalyl-acetic  acid,  which  does  not  have  a  symmetrical  formula 
as  usually  believed;  it  may  be  represented  by 


=  CH.CO.OH 
C6H4<     \0 

xx)/ 

which,   in   fact,   is   a   phthalide   derivative.    The   compound 
obtained  by  the  action  of  phthalic  anhydride  on  succinic  acid, 

CH2.CO.OH 
CH.CO.OH 

<.         CH2.CO.OH  /C.OH 

'        CH2.CO:OH 


3H<  =CeH<co>o 

\J  \J/        I 


TYPES  OF  SYNTHESES.  195 

is  immediately  decomposed  with  loss  of  water  and  carbon 
dioxide  to  form  a  double  lactone : 


There  also  exist  other  synthetic  methods,  in  which  the  for- 
mation of  compounds  belonging  to  the  aldol  type  play  an 
important  role.  The  preparation  of  coumarin,  by  heating 
phenol  with  malic  acid,  can  be  explained  by  admitting  the 
formation  of  the  aldehyde  of  malonic  acid  with  liberation  of 
formic  acid  : 

CO.OH  H  H.CO.OH 

CH.OH         +  OH-H20  =  CHO 

I  I 

CH2.CO.OH  CH2.CO.OH 

this  aldehyde  immediately  combines  with  phenol,  and  the  pro- 
duct so  formed  is  decomposed  into  water  and  coumarin: 


|  -2H20  = 

CH2.CO. 


CH(OH)  .C6H4.0H 

.OH  CH.CO- 


Benzaldehyde  also  condenses  with  benzyl  cyanide  in  the 
presence  of  sodium  alcoholate  : 


| 
=  C. 


CHO    CH2.CN  CH  =  C.CN 

It  is  not  impossible,  in  the  synthesis  of  hydrocarbons,  by 
the  aid  of  dehydrating  agents,  to  obtain  aromatic  aldehydes 


ORGANIC  SYNTHESES. 


and  hydrocarbons  with  formation  of  compounds  of  the  aldol 
type,  which  further  react  to  give  more  complicated  bodies. 
The  formation  of  diphenyl-ethane,  for  example,  from  aldehyde 
and  benzene  may  be  expressed  by  the  following  equations: 


CH3.CH(OH)  .C6H5  +  C6H6  =  CH3.CH(C6H5)  2  +  H20. 

A  solution  of  aldehyde  is  heated  with  a  large  quantity  of 
concentrated  sulphuric  acid,  and  the  theoretical  quantity  of 
benzene  is  added;  then,  after  some  hours'  standing,  the  hydro- 
carbon is  removed  with  water.  It  is  better  to  use  the  acetals 
than  the  aldehydes  themselves. 

Aldehydes  also  condense  with  different  derivatives  of  aro- 
matic hydrocarbons.  Thus,  if  a  well-cooled  mixture  of  aldehyde 
and  phenol  is  added  drop  by  drop  to  tin  chloride,  the  following 
reaction  takes  place  : 

CH3.CHO  +  2C6H5.OH  =  CH3.CH(C6H4.0H)  2  +  H20. 

Benzaldeyde,  heated  with  aniline  hydrochloride  in  the 
presence  of  zinc  chloride,  condenses  as  follows  : 

C6H5.CHO  +  2C6H5.NH2.HC1 

-C6H5.CH(C6H4.NH2.HC1)2  +  H20.1 

Phthalic  anhydride  condenses  with  phenols  in  the  same 
manner  as  aldehydes  and  ketones  in  the  presence  of  dehydrat- 
ing agents: 

co  C/(C6H,OH)2 

C6H4^       >0  +  2C6H5.OH=C6H4<      No  +H20. 

XXX  XXX 

1  The  hypothesis  that  compounds  of  the  aldol  type  are  at  first  obtained  is 
confirmed  by  the  fact  that  benzaldehyde  with  dimethylaniline,  in  the  presence 
of  a  mineral  acid,  reacts  according  to  the  following  equation,  giving  a  derivative 
of  benzhydrol: 

C6H5.CHO+  C6H5.N(CH3)2=  C6H5.CH(OH).C6H4.N(CH3)2. 


TYPES  OF  S  YNTHESES.  1 9  7 

The  reaction,  however,  may  be  different;  thus,  if  phenol  is 
added  to  a  heated  mixture  of  phthalic  anhydride  and  sulphuric 
acid,  hydroxy-benzoyl-benzoic  acid  1  is  formed,  which  then,  by 
loss  of  water,  forms  hydroxy-anthraquinone : 

/COX  /CO.C6H4.OH 

C6H4<        >0  +  C6H5.OH = C6H4< 

XJCK  XJO.OH 

/CO.C6H4.0H  /C(X 

C6H4<  -H20=C6H4<        >C6H3.OH. 

XCO.OH  XXX 

The  aromatic  compounds  also  condense  (with  loss  of  water) 
with  different  alcohols  of  the  aliphatic  and  aromatic  series. 
Benzene  with  benzhydrol  gives  triphenylme  thane.2  The  reac- 
tion only  takes  place  in  the  presence  of  dehydrating  agents. 
Usually,  a  mixture  of  the  reacting  bodies  with  P205,  ZnCl2,  or 
H2S04,  is  heated.  Thus,  nitro-benzyl  alcohol  condenses  with 
benzene  by  simply  shaking  with  concentrated  sulphuric  acidr 
to  give: 

'(1)  N02 


CeH4<\(3)  CH2.C6H5 

In  the  same  manner,  by  heating  to  250-300°  C.,  a  mixture 
of  aniline  (and  its  homologues,  or  their  salts)  with  ordinary 
alcohol  (or  its  homologues)  in  the  presence  of  zinc  chloride  or 
phosphoric  anhydride,  there  is  a  condensation  with  loss  of 
water : 

C6H5.NH2+C2H5.OH=C6H4</jp) 

1  A  similar  reaction  occurs  in  the  action  of  anhydrides  in  the  presence  of  alu- 
minium chloride.     If  a  small  amount  of  aluminium  chloride  is  added  to  a  hot 
solution  of  succinic  anhydride  in  benzene,  there  is  obtained: 

CH,.CO\  CH^CO.CeH, 

I    '        >0+C6H6=|    ' 
CH2.C(X  CH2.CO.OH 

2  Hemilian,  On  Some  Homologues  and  Isomerides  of  Triphenylmethane,  St. 
Petersburg,  1886  (in  Russian). 


198  ORGANIC  SYNTHESES. 

As  a  secondary  product,  there  is  sometimes  obtained  a 
secondary  base. 

It  is  interesting  to  note  the  formation  of  a-naphthylamine 
(from  the  condensation  of  aniline  with  furfuran)  by  heating 
pyromucic  acid,  aniline,  and  zinc  chloride  : 


XCH  =  CH  /CH=CH 

C6H5.NH2  +  0  |     =  C6H3(NH2)  |     +H20. 


Furfuran.  a-Naphthylamine. 

Aromatic  compounds  also  condense  with  various  acids.  By 
heating  acids  or  their  anhydrides  with  hydrocarbons  in  a  sealed 
tube,  together  with  phosphoric  anhydride,  ketones  are  produced: 

C6H6  +  C6H5.CO.OH  -  H20  =  C6H5.CO.C6H5. 

Phenols  react  more  easily  than  hydrocarbons;  dioxy-aceto- 
phenone  is  obtained  by  heating  to  150°  C.  glacial  acetic  acid 
with  resorcin  and  zinc  chloride  : 

-f  CH3.CO.OH=CH3.CO.C6H3/^ 


By  heating  aniline  with  acetic  anhydride  and  zinc  chloride, 
the  acetyl  group  enters  the  benzene  nucleus  and  also  the  NH2 
group,  and  there  is  formed  the  compound,  CHs.CO.CeH^NH. 
CO.CH3,  which,  on  saponification  with  acids,  gives  amido-ace- 

tophenone,  CH3.CO.C6H4.NH2. 

/OTT 
The    ammonia-aldehydes,    R.CH<^  -^-^  ,    readily    condense 

with  different  compounds  with  elimination  of  water.  With  a 
concentrated  aqueous  solution  of  hydrocyanic  acid,  they  form 

/CN 

aceto-acetic  ester  they  give  hydropyridine  derivatives:  thus, 
aldehyde-ammonia  with  aceto-acetic  ester  gives  the  ester  of 
hydrocollidine-dicarboxylic  acid  :  1 

1  N.  Liubavine,  The   Pyridine  Compounds,  Moscow,  1887  (in  Russian). 


nitriles  of  the  a-amido-carboxylic  acids,  R.CH<^   TTT  •     With 


TYPES  OF  SYNTHESES.  199 

CO.CH3  XOTT 

2 1  +CH3.CH<  vn  _3H20 

CH2.CO.O.C2H5 

=C5H2N(CH3)3(CO.O.C2H5)2. 

The  formation  of  the  ester  of  aceto-acetic  acid  and  its  ana- 
logues can  also  be  considered  as  a  condensation  with  elimina- 
tion of  water : 

CH3.CO.OH+CH3.CO.OH-H20=CH3.CO.CH2.CO.OH. 

This  condensation  is  produced,  with  elimination  of  alcohol, 
by  the  action  of  sodium  on  ethyl  acetate.  The  other  esters 
behave  in  a  similar  manner. 

Two  different  acids  may  also  be  condensed;  this  is  brought 
about  by  treating  a  mixture  of  the  two  esters  with  sodium  or 
sodium  alcoholate.  For  example,  by  using  an  ethereal  solution 
of  ethyl  oxalate  and  acetate,  there  is  obtained,  by  the  action 
of  sodium  ethylate,  C2H5,ONa,  a  sodium  salt  of  aceto-oxalic 
ester : 


CO.OC2H5 

+ CH3.CO.OC2H5 + C2H5.ONa 
O.OC2H5 


v/ 

i 


CO.OC2H5 

|  +2C2H5.OH. 

CO.CH(Na).CO.OC2H5 

With  a  mixture  of  ethyl  oxalate  and  succinate,  there  is  formed 
an  ester  of  succinyl-oxalic  acid,  a  tribasic  acid : 

CO.OC2H5    CH2.CO.OC2H5 

+  I  +C2H5.ONa  = 


io 


CO.OC2H5CH2.CO.OC2H5 
|  |  +2C2H5.OH. 

•C(Na).CO.OC2H5 


200  ORGANIC  SYNTHESES. 

In  the  aromatic  series,  benzoyl-benzoic  acid  offers  a  case 
analogous  to  that  of  aceto-acetic  acid.  The  hydroxy-benzoic 
acids  also  condense  directly  by  the  action  of  sulphuric  acid; 
only,  in  the  case  of  ketonic  acids,  there  are  formed  closed-chain 
compounds,  such  as  the  hydroxy-anthraquinones. 

The  condensation  of  acids  of  the  aromatic  series  with  those 
of  the  aliphatic  series  can  be  brought  about  by  means  of  the 
diazo-bodies.  The  ester  of  diazo-acetic  acid,  on  heating  with 
benzaldehyde  and  toluene,  gives  nitrogen,  N2,  and  the  ester  of 
benzoyl-acetic  acid: 

Nx 

1 1  >CH.CO.OH + C6H5.CHO  =  C6H5.CO.CH2.CO.OH + N2. 

W 

V.  CONDENSATION  WITH    LOSS    OF    HALOGEN   ACID,  OF 
A  METALLOID,  OR  OF  A  SALT. 

The  halogen  compounds  of  the  aliphatic  series,  and  those 
of  the  aromatic  series  containing  a  halogen  atom  in  the  side- 
chain,  react  with  hydrocarbons,  with  liberation  of  a  halogen 
acid: 

—  HI=CnH2n+i 


The  reaction  is  brought  about  by  heating  the  hydrocarbon  and 
halide  with  oxides  of  zinc,  magnesium,  and  calcium.  The 
aromatic  hydrocarbons  readily  combine  with  halogen  deriva- 
tives in  the  presence  of  zinc  dust,  or,  better,  in  the  presence  of 
aluminium  chloride  or  bromide : l 

C6H6 + 2CH3C1  -  2HC1  =  C6H4  (CH3)  2. 

This  reaction  takes  place  with  such  regularity  that  different 
isomers  can  be  obtained  at  will.  With  aluminium  chloride  the 
principal  derivatives  are  meta,  with  zinc  dust  para  and  ortho. 

If  the  halogen  compound  is  gaseous,  like  methyl  chloride, 
it  is  passed  into  the  heated  hydrocarbon  to  which  aluminium 

1  The  chlorides  of  iron  and  zinc  act  in  the  same  manner. 


TYPES  OF  SYNTHESES.  201 

chloride  has  been  added;  if  it  is  liquid,  it  is  mixed  with  the  hydro- 
carbon, and  the  metallic  chloride  is  added  little  by  little  until  the 
halogen  acid  is  no  longer  liberated. 

When  the  reaction  is  finished,  the  product  is  washed  with 
water  and  then  fractionated,  for  there  is  always  obtained  a 
mixture  of  several  hydrocarbons.  Thus,  benzene,  treated  with 
methyl  chloride  besides  methyl-benzene,  C6H5.CH3,  also  gives, 
a  whole  series  of  methyl-benzenes  up  to  the  hexa  compound,. 
C6(CH3)6,  inclusively.  This  process  is  never  complete,  as  by 
the  action  of  the  aluminium  chloride  a  reverse  reaction  earn 
take  place: 

C6H5.CH3 + HC1  -  C6H6 + CH3C1. 

Zinc  chloride  acts  much  more  slowly  than  aluminium  chlor- 
ide; nevertheless,  in  certain  cases,  it  is  preferable  (for  example, 
with  naphthalene  and  benzyl  chloride,  CeHs.CH^.Cl),  for  then 
less  secondary  products  are  obtained.  Metallic  zinc  only  reacts 
by  being  converted  into  zinc  chloride  at  the  expense  of  the 
chlorine  compound. 

In  place  of  chlorine  derivatives,  the  bromine  or  iodine 
compounds  may  also  be  used.  With  the  latter  it  is  necessary 
to  heat  in  a  sealed  tube  with  a  small  quantity  of  iodine. 

Normal  propyl  bromide,  CH3.CH2.CH2.Br,  on  condensing 
with  benzene  under  the  influence  of  aluminium  bromide,  gives 
isopropyl-benzene,  (CH3)2.CH.C6H5,  for  by  the  action  of  alumin- 
ium bromide  alone  this  same  bromide  is  converted  into  isopropyl 
bromide.  Allyl  chloride,  CH2:CH.CH2.C1,  with  benzene  and 
aluminium  chloride,  does  not  give  allyl-benzene,  but  diphenyl- 
propane  (C6H5)2.C3H6.1 

1  There  is  consequently  a  substitution  of  chlorine  by  C6H5  and  a  fixation  of 
C6H6.  An  analogous  case  presents  itself  in  the  action  of  ethylene  on  benzene 
in  the  presence  of  aluminium  chloride,  this  even  being  a  good  method  for  the 
preparation  of  ethyl  benzene: 

C2H4+C6H6=C6H5.C2H5. 

This  reaction  may  be  explained  by  admitting  that  the  C3H4  is  first  converted 
into  C2H5C1,  which  then  reacts  with  C6H6. 

According  to  Friedel  and  Crafts,  in  syntheses  with  the  aid  of  aluminium  chlo- 


202  ORGANIC  SYNTHESES. 

Aromatic  acids  containing  a  halogen  in  the  side-chain  also 
condense  with  the  aromatic  hydrocarbons  in  the  presence  of 
the  halogen  salts  of  aluminium : 

C6H5.CH.  (Br.)CO.OH + C6H6  =  HBr  +  (C6H5)2.CH.CO.OH. 

Bodies  containing  several  halogen  atoms  behave  in  the 
same  manner  with  hydrocarbons  in  the  presence  of  aluminium 
chloride  as  monohalogen  derivatives.  Chloroform  with  Al2Cl6 
reacts  with  3C6H6  to  give  triphenylme thane,  CH(C6H5)3.  This 
process,  in  fact,  is  used  for  the  preparation  of  the  latter  body; 
as  a  secondary  product,  diphenylme thane,  CH2 (Cells)  2,  is 
formed. 

With  carbon  tetrachloride  and  benzene,  in  the  presence  of 
aluminium  chloride,  C14  is  not  replaced  by  (C6H5)4,  as  would 
at  first  be  thought;  only  3C1  are  replaced,  and  CC1(C6H5)3, 
triphenyl-chlor-methane,  is  formed.  Acetylene  tetrabromide 
with  benzene  and  aluminium  chloride  gives  anthracene  anji  a 
small  quantity  of  triphenyle thane  and  brom-benzene : l 

CH.Br2 

|  +2C6H6=4HBr+C6H4 

CH.Br2 

ride  there  is  formed  an  organo- metallic  compound  (which  they  have  not  been 
able  to  isolate,  however)  between  A12C16  and  the  benzene  (or  other  hydrocarbon), 
with  liberation  of  hydrochloric  acid: 

C6H5.  A12C15=  A12C16+  C6H6-HCL. 

This  compound  then  reacts  with  halogen  derivatives,  regenerating  A12C16.  Accord- 
ing to  Gustavsonn,  however,  by  the  action  of  A12C16  on  aromatic  hydrocarbons, 
condensation  products  are  formed,  as,  for  example,  A12C16.6C6H6.  During  their 
formation  there  would  be  considerable  heat  liberated  which  would  account  for 
their  strongly  increased  reactivity. 

1  An  interesting  formation  of  derivatives  of  triphenylethane  is  in  the  con- 
densation of  phenols  with  the  dichlor-esters.  If  the  phenol  is  intimately  mixed 
with  the  dichlor-ester,  the  mixture  heats  up,  a  brisk  reaction  takes  place,  with 
liberation  of  hydrochloric  acid  and  ethyl  chloride.  With  an  excess  of  phenol 
a  reddish-colored  resinous  substance  is  obtained  soluble  in  alkalies.  The  re- 
action may  be  thus  expressed: 

CH2.C1  CH2.C6H..OH 

I  +  3C.H,.OH=|  +2HC1+C2H5OH. 

CHC1.0C2H5  CH(C6H4OH)2 

Dichlor-ester.         Phenol.  Trihydroxy- 

triphenylethane. 


TYPES  OF  SYNTHESES.  203 

Phenols,  in  the  presence  of  zinc  dust  or  zinc  chloride,  react 
like  hydrocarbons  with  the  halogen  compounds  : 

C6H5.CH2C1  +  C6H5.OH  =  C6H5.CH2.C6H4.OH  +  HCL 

Phenol  with  carbon  tetrachloride  and  a  small  quantity  of  zinc 
chloride  gives  aurine  : 

CC14  +  3C6H5.OH  =  (C6H4.OH)2C/  1  °     +4HC1. 

X0 

The  halogen  compounds  condense  very  readily  with  tertiary 
amines  : 


This  reaction  is  carried  out  on  a  water-bath  without  any  con- 
densing agent. 

The  acid  chlorides  of  both  the  aliphatic  and  aromatic  series 
condense  with  hydrocarbons  (in  the  presence  of  aluminium 
and  zinc  chlorides)  to  form  ke  tones  : 

f 
C6H5.CO.C1  +  CioH8  =  C6H5.CO.Ci  0H7  +  HCL 

Two  molecules  of  the  acid  chloride  and  one  molecule  of  the 
hydrocarbon  may  also  take  part  in  the  reaction  : 


2C6H5.CO.C1  +  C6H2(CH3)4  -  C6(CH3)4'         +  2HC1. 


Chlorides  of  dicarboxylic  acids  react  with  either  one  or  two 
molecules  of  the  hydrocarbon;  thus,  the  chloride  of  isophthalic 
acid  with  one  molecule  of  benzene  gives : 

(1)  CO.C6H5. 

(3)  CO.C1      ' 


204  ORGANIC  SYNTHESES. 

while  with  two  it  gives  isophthalophenone: 

(l)CO.C6H5 


Phthalyl  chloride  with  benzene,  in  the  presence  of  aluminium 
chloride,  gives  phthalophenone  : 

C  (C6H5)2 


The  preparation  of  the  above  ketones  is  carried  out  by  gradu- 
ally adding  aluminium  chloride  to  a  mixture  of  the  acid  chloride 
and  the  hydrocarbon  until  there  is  no  further  liberation  of 
hydrochloric  acid. 

Carbonyl  chloride,  in  the  presence  of  aluminium  chloride, 
reacts  with  hydrocarbons  in  the  same  manner  -as  the  acid  chlor- 
ides. With  benzene  it  gives  benzoyl  chloride  : 

CO.C12  +  C6H6  =  C6H5.CO.C1  +  HC1. 

But,  as  benzoyl  chloride  reacts  in  turn  on  benzene,  the  final 
product  is  benzophenone  : 

C6H5.CO.C6H5. 

Dimethyl-aniline,  at  50°  C.,  reacts  with  carbonyl  chloride  to 
give  dimethyl-amido-benzoic  acid,  or,  rather,  its  chloride  : 


The  chlorine  derivatives  of  the  substituted  carbamic  acids, 
Cl.CO.NHR,  with  the  aromatic  hydrocarbons,  (for  example,  tolu- 
ene, C6H5.CH3)  give  the  substituted  amides  of  the  aromatic  acids  : 

/(l)CH» 

co  NHR 


This  is  one  of  the  methods  of  synthesizing  the  aromatic  acids. 


TYPES  OF  SYNTHESES.  205 

Cyanogen  chloride,  in  the  presence  of  aluminium  chloride, 
reacts  with  benzene  to  give  benzo-nitrile,  CeH5.CN. 

The  reaction  of  the  aliphatic  acid  chlorides  with  aluminium 
chloride  is  of  interest.1  Thus,  acetyl  chloride,  diluted  with 
chloroform,  reacts  with  aluminium  chloride  at  40-45°  C.,  lib- 
erating a  large  amount  of  hydrochloric  acid  gas,  and  forming 
a  white  crystalline  substance  having  a  composition  of  Ci2Hi4 
06A12C18,  the  formation  of  which  may  be  expressed  by  the 
equation  : 

6(C2H3OC1)  +  A12C16  =  4HC1  +  C21H1406A12C18. 

This  organo-metallic  compound  is  decomposed  with  alcohol 
into  diace  to-acetic  acid  ester: 


Benzyl  cyanide,  C6H5.CH2.CN,  easily  replaces  the  hydrogen 
in  the  CH2  group  in  the  presence  of  halogen  compounds.  Thus, 
by  the  action  of  benzyl  chloride,  C6H5.CH2C1,  and  sodium  alco- 
holate,  with  benzyl  cyanide,  there.  is  obtained  the  compound: 


By  gently  heating  a  mixture  of  benzyl  cyanide,  sodium,  and 
methyl  iodide,  there  is  produced  the  nitrile  of  hydro-atropic 
acid: 


The  metallic  cyanides  (KCN,  NaCN,  ferrocyanides,  etc.)  react 
with  the  halogen  compounds  of  the  aliphatic  series  and  with 
alkyl  acid  sulphates,  forming  nitriles.  The  reaction  is  ordinarily 
brought  about  by  a  prolonged  boiling  of  the  solution  of  halogen 

1  See  Jour.  Soc.  Phys.  Chim.  Russe,  vol.  20,  p.  81. 


206  ORGANIC  SYNTHESES. 

compound  and  cyanide  in  dilute  alcohol.  The  nitriles  are 
isolated  and  purified  by  distillation;  often  they  are  not  isolated, 
but  by  saponification  are  converted  directly  into  carboxylic 
acids.  The  tertiary  halogen  compounds  react  with  difficulty 
with  the  alkaline  cyanides;  the  latter  are  replaced  by  the 
double  cyanide  of  mercury  and  potassium,  Hg(CN)2.2KCN. 

Aromatic  compounds  containing  a  halogen  in  the  side- 
chain  also  react  with  metallic  cyanides  : 

C6H5.CH2C1  +  KCN  =  C6H5.CH2.CN  +  KC1. 

If  dilute  alcohol  is  used  as  a  solvent,  the  amide  of  phenylacetic 
acid,  CeH5.CH2.CO.NH2  is  obtained  as  a  secondary  product. 
To  convert  the  chloride  of  triphenyl-carbinol,  (C6H5)3.CC1,  into 
the  nitrile,  it  is  heated  with  mercury  cyanide,  Hg(CN)2,  to  150- 
170°  C. 

Halogens  in  the  aromatic  nucleus  are  replaced  by  CN  only 
with  difficulty,  and  never  completely,  even  at  300-400°  C.;  by 
using  potassium  ferrocyanide,  the  reaction  takes  place  very 
incompletely.  The  iodine  compounds  react  somewhat  more 
readily,  than  the  other  halogen  derivatives. 


Brom-benzyl  bromide,  CeH       £  Q-  -gr,  on  boiling  with 
potassium   cyanide,  is   converted   into   brom-benzyl   cyanide, 
Phenyl-brom-acetic  acid,  on  boiling  with 


potassium  cyanide,  loses  its  bromine  and  is  converted  into 
diphenyl-succinic  acid  : 

2C6H5.CHBr.CO.OH  +2KCN  =  2KBr  +  (CN)2  + 

C6H5.CH.CO.OH 

I 
C6H5.CH.CO.OH 

In  the  aromatic  series,  the  nitriles  are  generally  obtained 
through  the  intervention  of  the  sulphonic  acid  derivatives  by 
heating  the  latter  with  pure  potassium  cyanide,  or  with  potas- 


TYPES  OF  SYNTHESES.  207 

slum  ferrocyanide.  If  necessary,  the  reaction  may  be  carried 
out  in  an  atmosphere  of  carbon  dioxide.  The  nitrile  is  isolated 
by  distillation: 


These  bodies  may  also  be  obtained  by  replacing  NH2  with 
CN  with  the  aid  of  the  azo  compounds.  Benzonitrile,  for  ex- 
ample, is  obtained  by  slowly  adding  with  agitation  the  solution 
of  the  diazo  chloride,  heated  to  90°  C.,  to  the  double  cyanide 
of  copper  and  potassium.  This  double  cyanide  is  prepared  by 
adding  25  gms.  of  a  96  per  cent,  solution  of  potassium  cyanide 
to  a  boiling  solution  of  25  gms.  of  copper  sulphate  in  150  cc. 
of  water. 

The  acid  chlorides  and  bromides  also  react,  on  heating,  with 
metallic  cyanides  :  * 

CH3.CO.C1  +  Ag.CN  =  CH3.CO.CN  +  AgCl. 

Although  the  alkaline  cyanides,  potassium  ferrocyanider 
and  the  double  cyanide  of  mercury  and  potassium,  and  some 
others,  with  the  halogen  compounds,  give  principally  nitriles, 
other  cyanides,  such  as  those  of  silver  and  zinc  and  other  analo- 
gous ones,  form  principally  isonitriles  or  carbylamines.  The 
reaction  is  carried  out  at  100°  C.: 

CH3I  +  AgCN  =CH3NC  +  Agl. 

To  obtain  the  carbylamines,  for  each  molecule  of  iodide 
there  are  taken  two  molecules  of  silver  cyanide,  one  of  which 
serves  for  the  formation  of  a  double  compound  with  the  iso- 
nitrile,  which  is  subsequently  decomposed  with  water  and 
potassium  cyanide.  The  carbylamine  is  purified  by  distillation. 

1  For  the  preparation  of  the  nitriles,  see  page  117;  for  the  substitution  of  OH 
by  CN,  see  page  198;  for  the  combination  with  HCN,  see  page  187;  and  for  the 
action  of  CNC1,  see  page  205. 


-2o8  ORGANIC  SYNTHESES. 

With  isopropyl  iodide,  (CH3)2CHI,  and  silver  cyanide,  besides 
the  carbylamine,  (CH3)2CH.NC,  there  are  also  formed,  as  second- 
ary products,  propylene  and  hydrocyanic  acid. 

The  carbylamines  are  easily  obtained  by  the  energetic  reac- 
tion of  alcoholic  potash  on  a  mixture  of  chloroform  and  a  salt 
of  an  amine l : 

CHC13  +  NH2.CH3 + 3KOH  =  CH3.NCN  +  3KC1  +  3H20. 

Jt  is  on  this  formation  of  carbylamine  that  is  based  the  charac- 
teristic reaction  for  chloroform. 

Compounds  which  contain  the  groups,  CO.CH2.CO  or 
CO.CHR.CO,  can  have  the  hydrogen  of  these  groups  easily 
replaced  by  sodium,  and  these  sodium  derivatives  which  are 
formed  exchange  the  metal  for  an  R  group  by  the  action  of 
the  halogen  compound  of  the  aliphatic  series,  and,  in  certain 
cases,  of  the  aromatic  series.  Ace  to-acetic  ester,  malonic  ester, 
and  others  can  have  one  or  two  atoms  of  hydrogen  replaced  by 
a  radical. 

The  manner  of  procedure  is  the  following:  A  calculated 
quantity  of  sodium  in  the  least  possible  amount  of  absolute 
alcohol  is  added  to  the  ester,  and  afterwards,  with  cooling  if 
necessary,  the  theoretical  quantity  of  the  halogen  compound; 
finally,  the  reaction  is  finished,  if  required,  by  heating  in  a  flask 
with  a  return  condenser  until  the  liquor  is  no  longer  alkaline. 
The  alcohol  is  distilled  off,  and  the  product  is  washed  with 
water  to  remove  any  halogen  salt,  and  the  ester  is  finally  puri- 
fied by  distillation.  If  an  acid  chloride  is  allowed  to  act  on  the 
sodium  compound,  it  is  necessary  to  operate  in  an  ethereal 
solution.  For  the  preparation  of  diaceto-acetic  ester,  as  much 
sodium  as  possible  is  dissolved,  and  there  is  added  little  by  little 
an  ethereal  solution  of  acetyl  chloride,  taking  a  quantity  cor- 
responding to  the  sodium  dissolved. 

To  obtain  compounds  containing  two  radicals,  it  is  not 

CH  V 

1  Alexeyeff  gives  the  formula  of  the  isonitrile  as  I        >N. 

CH/ 


TYPES  OF  SYNTHESES.  209 

always  necessary  to  isolate  the  first  body  containing  a  single 
radical.  After  adding  for  each  molecule  of  alcoholate  a  cal- 
culated amount  of  the  halogen  compound,  and  when  it  is  no 
longer  alkaline,  a  second  molecule  of  alcoholate  may  be  added, 
followed  by  the  addition  of  the  halogen  body.  This  reaction 
is  of  great  importance  in  syntheses,  and  is  applied  in  a  large 
number  of  cases. 

Dike  tones  which  contain  CO.CH2.CO,  and  compounds  which 
have  S02.CH2.CO,  behave  like  ace  to-acetic  ester  towards  the 
alcoholates  and  the  halogen  compounds. 

Condensation,  with  the  production  of  metallic  halogen 
derivatives,  takes  place  by  the  action  of  the  organo-metallic 
compounds  on  halogen  compounds: 

CHBr  CH.C2H5 

2  1 1         +  (C2H6) 2Zn  =  2  1 1  +  ZnBr2. 

CH2  CH2 

C6H5.CH.C12  +  Zn(CH3)2  =  C6H5.CH(CH3)2  +  ZnCl2. 

The  reaction  is  so  energetic  that  it  is  necessary  to  moderate 
it  by  dilution  with  ether,  benzene,  etc. 

Dichlor-ethyl-ether  with  zinc-ethyl  only  replaces  one  atom 
of  chlorine  and  forms : 


CH2.C1 

.OC2H5 


Amp 


to  replace  the  second,  it  is  necessary  to  heat  in  a  sealed  tube. 

The  acid  chlorides  react  very  readily  with  the  organo- 
metallic  compounds  to  form  ketones,  a  result  obtained  by  the 
further  action  of  the  acid  chloride  on  the  first  product  of  the 
direct  action.  The  reaction  may  be  expressed  by  the  following 
equation : 

2CH3.CO.C1  +  Zn(CH3)  2 = 2CH3.CO.CH3  +  ZnCl2. 


210  ORGANIC  SYNTHESES. 

It  is  necessary,  after  the  reaction  is  finished,  to  treat  the 
product  with  water  or  a  dilute  acid,  especially  when  there  is  an 
excess  of  ZnR2;  otherwise  it  would  form  tertiary  alcohols. 
When  the  substances  are  mixed  together,  they  should  be  cooled. 

The  iodine  compounds,  when  treated  with  sodium,  nearly 
all  behave  according  to  the  following  equation  : 


RI+R'I+Na2  =  R.R' 


Usually  the  reaction  takes  place  less  readily  with  chlorine 
and  bromine  compounds. 

In  certain  cases,  by  employing  a  mixture  of  halogen  com- 
pounds, the  reaction  takes  place  separately  on  each  one;  this 
is  particularly  true  when  the  bodies  are  not  attacked  with  the 
same  energy.  Thus,  on  heating  a  mixture  of  octyl  bromide  and 
ethyl  iodide  with  sodium,  the  latter  is  converted  entirely  into 
butane  before  the  temperature  becomes  sufficiently  elevated  to 
attack  the  octyl  bromide;  also  the  latter  is  converted  entirely 


Bodies   containing  several  halogen  atoms  behave  in  the 
same  manner  as  those  which  only  contain  one  : 

+2CH3.CH2.CH2.Br  +2Na2  = 


In  general,  the  sodium  is  allowed  to  act  on  the  mixture  of 
the  well-dried  halogen  compounds,  and  without  alcohol.  The 
mixture  is  cooled,  if  necessary,  or,  on  the  other  hand,  heated 
under  a  certain  pressure.  With  secondary  iodides  there  may  be 
formed  unsaturated  hydrocarbons,  but  it  is  easy  to  separate 
these  by  shaking  with  sulphuric  acid. 

In  the  aliphatic  series,  the  synthesis  of  the  carboxylic  acids 
and  their  esters  is  carried  out  in  the  same  manner.  Sometimes 
the  sodium  is  replaced  with  silver  obtained  by  the  action  of  zinc 


TYPES  OF  SYNTHESES.  211 

on  silver  chloride.  Valerianic  acid  is  obtained  in  this  manner 
by  heating  /3-iodo-propionic  acid  and  ethyl  iodide  with  silver  at 
150-180°  C.: 


/?-Iodo-propionic  acid  alone  with  silver  gives  adipic    acid. 
With  silver  and  (CeHs^CCl^  we  have  the  reaction: 


C(C6H5)2 

2(C6H5)2C.Cl2+2Ag2  =  ||  +4AgCl. 

C(C6H5)2 

The  silver  may  be   replaced  by  other  metals.    Thus  the 
reaction, 


C6H5Br  +CH2CLCO.OC2H5  -  (Br  +C1)  =C6H5.CH2.CO.OC2H5, 

occurs  on  heating  with  copper  at  200°  C.  Brombenzene  reacts 
with  ethyl  chlor-formate,  C1CO.OC2H5,  on  heating  with  sodium 
amalgam  of  1  per  cent. 

Condensations  with  removal  of  halogen  may  also  take  place 
with  the  aid  of  alkaline  cyanides  (see  page  206)  . 

Condensation  with  elimination  of  a  halogen  acid  takes  place 
in  certain  cases  through  the  action  of  an  alcoholic  solution  of 
sodium.  Thus,  para-nitro-benzyl  chloride  gives  dinitro-stilbene  : 

(4)  N02  HC.C6H4.N02 


1)  CH2C1  HC.C6H4.N02 

As  an  example  of  a  condensation  with  elimination  of  a  salt, 
may  be  given  the  formation  of  ketones  by  the  distillation  of 
certain  salts;  thus,  ordinary  acetone  is  obtained  according  to 
the  following  equation  : 

MO\ro+CH3\co  -  MO\ro+CH3\x> 

CH3/°    +MO/C        MO/°    +CH3/°U' 


212  ORGANIC  SYNTHESES. 

and  benzophenone,  in  the  same  way,  may  be  prepared  from 
benzoates  : 


C6H5.CO.OM  +  MO.CO.C6H5  =  CO/9    + 


The  synthesis  of  the  aromatic  carboxylic  acids,  by  the 
fusion  of  a  mixture  of  an  aromatic  sulphonic  acid  and  a  for- 
mate, is  also  a  condensation  with  elimination  of  a  salt  : 

C6H5.S03M  +  HCO.OM  =  C6H5(CO.OM)  +  HMS03. 


VI.     CONDENSATION  WITH  LIBERATION  OF  HYDROGEN. 

The  reaction  expressed  by  the  general  equation, 

R.H + R.H  +  0  =  R.R  +  H20, 

often  occurs  in  the  aromatic  series.  Benzene,  for  example, 
among  other  products,  gives  diphenyl  when  its  vapors  are 
passed  through  an  iron  tube  heated  to  redness  and  filled  with 
pumice-stone.  The  formation  of  diphenyl  will  explain  the 
production  of  a  certain  quantity  of  benzoic  acid  in  the  oxida- 
tion of  benzene  with  manganese  dioxide  and  sulphuric  acid. 
Naphthalene,  by  the  same  reaction  as  above,  gives  CioH7.CioH7. 
Dimethyl-aniline,  dissolved  in  sulphuric  acid  and  oxidized 
with  lead  oxide,  is  converted  into  tetramethyl-benzidine : 


C6H4.N(CH3)2 
6H4.N(CH3)2' 


v_ 

A 


Phenol,  on  oxidation  with  potassium  permanganate,  gives 
symmetrical  diphenol: 

C6H4.OH 
C6H4.OH' 


TYPES  OF  SYNTHESES.  215 

Resorcin  and  hydroquinone,  fused  with  alkalies,  are  con- 
verted into : 

C6H3(OH)2 
6H3(OH)2' 

The  other  phenols,  oxy-aldehydes,  and  oxy-acids  of  the 
aromatic  series  behave  in  a  similar  manner.  Vanillin,  with  a 
hot  solution  of  ferric  chloride,  gives  divanillin : 1 

[C6H2(COH)(OCH3)OH]2. 

An  aqueous  solution  of  vanillin  gives  a  bluish-violet  colora- 
tion with  ferric  chloride;  if  heated,  the  divanillin  is  deposited 
in  the  form  of  a  white  crystalline  substance,  difficultly  soluble 
in  the  ordinary  solvents,  but  readily  so  in  alkalies. 

Gallic  acid,  oxidized  with  silver  oxide  or  arsenic  acid,  gives- 
the  acid: 

C6H(OH)3CO.OH 
C6H(OH)3CO.OH* 

In  certain  cases,  hydrogen  may  be  removed  indirectly. 
Thus,  iodine,  acting  on  the  sodium  compound  of  bodies  con- 
taining the  group,  CO.CH2.CO,  splits  off  sodium,  and  there  is- 
formed  a  condensation: 

CH3.CO.CHNa  CH3.CO.CH.CO.OC2H5 

2  +I2=  |  +2NaI. 

CO.OC2H5          CH3.CO.CH.CO.OC2H5 

This  reaction  takes  place  by  dissolving  the  sodium  com- 
pound in  ether  and  adding  the  theoretical  quantity  of  a  con- 
centrated solution  of  iodine  in  ether. 

A  Dianine,  Conversion  of  Phenols  into  Diphenols  by  Oxidation,  St.  Petersburg, 
1880  (m  Russian). 


214  ORGANIC  SYNTHESES. 

VII.    CONDENSATION  WITH  LIBERATION  OF  WATER  AND 

HYDROGEN. 

This  reaction  takes  place  in  the  important  synthesis  of 
Skraup,  —  the  formation  of  quinoline  and  its  derivatives  by  heat- 
ing various  amido  compounds  with  glycerol  and  sulphuric  acid.1 
Quinoline  is  obtained  in  the  dry  distillation  of  the  condensa- 
tion product  of  acrolein  with  aniline  : 

N  =  CH 
C6H5.N:CH.CH.CH2(?)          ->   C6H4 


and  it  is  known  that  sulphuric  acid  acting  on  glycerol  will  give 
acrolein.  In  the  reaction  of  Skraup,  the  removal  of  hydrogen 
can  be  admitted  in  the  product  of  condensation  (with  loss 
of  water)  of  acrolein  with  amido  compounds.  The  hydrogen 
which  is  so  liberated  may  act  as  a  reducing  agent;  hence  there 
is  added  to  the  mixture  an  oxidizing  agent  such  as  nitrobenzene, 
or,  better,  sodium  nitrophenate.  The  general  method  of  obtain- 
ing the  quinolines  consists  in  heating  for  several  hours,  with  a 
reflux  condenser,  the  amido  compounds  with  glycerol  and  sul- 
phuric acid,  with  some  nitrobenzene.  The  latter  is  removed 
by  distillation  in  steam;  the  remaining  liquor  is  made  alkaline, 
and  the  free  base  is  removed  either  by  distillation  in  steam  or 
by  ether.  Nearly  all  aromatic  compounds  give  quinoline  deriva- 
tives if  they  contain  an  unre  placed  hydrogen  in  the  ortho  position 
with  reference  to  the  amido  group. 

VIII.     CONDENSATION  WITH  LIBERATION  OF  C02. 

The  formation  of  ketones  (see  page  211)  falls  under  this 
class  of  condensations,  as  well  as  many  other  cases. 

Sulphuric  acid  acting  on  malic  acid  gives  cumalic  acid  : 

2C4H605  -  2H20  -  2H2  -  2C02  =  C6H404  =  C5H302.CO.OH. 

The  cumalic  acid  may  be  considered  as  a  condensation  product 
of  malonic  aldehyde. 

1  See  the  Mpnograph  of  Liubavine  cited  on  p.  198. 


TYPES  OF  SYNTHESES  215 

Tartaric  acid,  on  dry  distillation,  or  by  the  action  of  hydro- 
chloric acid  at  180°  C.,  gives  pyrotartaric  acid: 

2C4H606 = C5H804  +  3C02 + 2H20. 

Oxalic  acid,  reduced  with  sodium  amalgam,  gives  desoxalic 
acid: 

HO.C(CO.OH)2 
3C2H204-C02-02=C5H6OH=        | 

HO.CH.CO.OH 

The  electrolysis  of  aliphatic  acids  is  effected  with  the  lib- 
eration of  carbonic  acid  and  hydrogen  with  a  condensation  of 
the  hydrocarbon  groups  which  form  a  part  of  the  acid  radical. 
The  electrolysis  of  the  salts  of  valeric  acid  gives  octane. 

IX.   POLYMERIZATION. 

Sometimes  polymerization  is  the  result  of  an  indirect  com- 
plication of  the  molecule;  in  other  cases  it  is  the  result  of  a 
series  of  consecutive  reactions;  while,  in  others  still,  it  is  the 
result  of  direct  condensation.  The  latter  case  takes  place  most 
often  by  the  action  of  high  temperatures  on  unsaturated  bodies: 
acetylene  gives  benzene;  valerylene  and  isoprene  give  the  ter- 
pene,  CioHie;  the  terpenes  themselves  are  converted  into 
C20H32,  etc.  Styrol  is  converted  into  its  polymeride,  metastyrol. 

Certain  bodies  bring  about  polymerization  by  their  simple 
presence.  Terpenes  polymerize  under  the  influence  of  boron 
fluoride,  antimony  trichloride,  etc. 

The  polymerization  of  cyanic  acid  into  cyanuric  acid  l  is 
the  result  of  an  indirect  condensation,  the  nitrogen  binding 
the  groups  together.  The  structure  of  cyanuric  acid  is : 

C.OH 

N/\N 


HO.CV/C.OH 

N 


1  The  action  of  triethyl  phosphine,  P(C2H5)3,  on  phenylcyanate,  CN.OC6H£, 
is  interesting;  a  minute  quantity  of  the  former  is  sufficient  to  convert  a  very 
large  quantity  of  the  latter  into  cyanuric  ester,  C3N3(OC6H6)3, 


216  ORGANIC  SYNTHESES. 

An  analogous  formula  is  admitted  for  cyanphenine,  the 
polymer  of  benzonitrile,  (C6H5.CN)3,  which  is  formed  not  only 
by  the  action  of  sodium  on  benzonitrile,  but  also  by  the  action 
of  sodium  on  the  ethereal  solution  of  a  mixture  of  C3N3C13  and 
brombenzene : 

3C6H5Br +C3N3C13  +3Na2  =  (C6H5)3C3N3  -f-NaCl +3NaBr. 

An  entirely  different  case  is  presented  in  the  polymeriza- 
tion of  nitriles  of  the  aliphatic  series  by  the  action  of  metallic 
sodium;  there  is  here  a  direct  condensation.  The  polymerized 
nitriles  are  found  to  be  related  to  the  pyrimidine  derivatives,1 
which  are  obtained  by  the  condensation  of  amidines  with  aceto- 
acetic  ester.  Cyanethine,  for  example,  very  probably  has  the 
formula : 

N-C.C2H5 

/        \ 
C2Ii5.C  C.CH3. 

N  =  C.NH2 

There  has  also  been  obtained  a  double  nitrile,  C6Hi0N2r 
intermediate  between  propionitrile  and  cyane thine. 

1 1.  Ponomareff,  On  the  Constitution  of  Cyariuric  Acid,  Odessa,  1885  (in  Russian)* 


CHAPTER  IX. 
ISOMERIZATION. 

IT  sometimes  happens  that  a  body  is  converted  into  an 
isomeric  form  possessing  the  same  percentage  composition, 
either  by  the  same  reaction  which  gives  rise  to  the  first  body, 
or  to  some  other  reaction.  This  displacement  of  the  atoms 
combined  in  a  molecule  can  be  explained  either  by  the  fact  of 
successive  reactions,  or  by  the  existence  of  a  more  stable  form 
to  which  all  the  other  isomers  tend  to  transform  themselves.1 
This  latter  supposition  has  been  used  in  order  to  explain  the 
tendency  possessed  by  various  hydrocarbons  to  pass  into  their 
isomers  having  a  symmetrical  structure.  For  example,  the 
butylenes  tend  to  pass  into 

CH3.CH:CH.CH3. 

But  this  fact,  as  well  as  the  transformation  of  propyl  bro- 
mide, CH3.CH2.CH2Br,  into  isopropyl,  (CH3)2CHBr,  by  the 
action  of  aluminium  bromide,  the  formation  of  secondary 

1  A.  Eltekoff,  Molecular  Transpositions  among  the  Hydrocarbons  of  the  Ethylene 
Series  and  among  the  Saturated  Alcohols,  Karkoff,  1884  (in  Russian).  See  also 
the  theses  of  Gustavsonn  and  Ponomareff,  cited  on  pp.  75  and  216. 

In  some  cases,  the  presence  of  certain  groups  in  the  molecule  may  be  the 
cause  of  its  isomerization.  Vidmann  and  Fileti  have  shown  the  existence  of 
certain  rules  in  this  respect.  In  the  benzene  derivatives,  if  the  group 
CH2.CH2.CH3  is  found  in  the  para  position  with  reference  to  a  CII3  group,  the 
oxidation  of  the  latter  group  (conversion  into  CH2OH,  CHO,  or  CO. OH)  is 
accompanied  by  the  transposition  of  the  CH^CH^CHg  group  into  CH(CH3)2. 
Inversely,  the  reduction  of  the  groups  CH2OH,  CHO,  or  CO.  OH  to  CH3  con- 
verts CH(CH3),  into  CH2.CH2.CH3. 

217 


218  ORGANIC  SYNTHESES. 

butyl  alcohol  in  place  of  the  normal,  and  the  tertiary  in  place 
of  isobutyl  alcohol,  can  be  explained  more  readily  by  successive 
fixations  and  removals  of  groups. 

The  isomerization  of  acetylene  hydrocarbons,  when  they 
are  heated  with  alkalies  in  alcoholic  solution,  really  takes  place, 
as  shown  by  Favorsky,1  by  the  fixation  and  then  the  removal 
of  the  alcoholate.  Thus  ethyl  acetylene,  CH3.CH2.C  =  CH, 
heated  to  170°  C.  with  an  alcoholic  solution  of  caustic  potash, 
gives  dimethyl  acetylene,  CH3.C  =  C.CH3.  In  this  same  manner 
the  different  cases  of  isomerism  above  noted  may  be  explained. 

Durol,  or  tetramethyl-benzene  (symmetrical),  C6H2(CH3)4, 
by  the  action  of  sulphuric  acid,  is  converted  into  adjacent  tetra- 
methyl-benzene. There  is  in  this  case  an  instance  of  successive 
reactions,  for  at  the  same  time  there  are  formed  sulphonic 
acids  of  the  two  hydrocarbons  and  of  trimethyl-benzene,  and, 
still  further,  hexamethyl-benzene.  When  brom-tribrom-phenol, 
C6H2Br3.OBr,  is  heated  to  180°  C.  with  concentrated  sul- 
phuric acid,  it  is  converted  into  the  isomer,  tetrabrom-phenol, 
C6HBr4.OH. 

The  compounds,  CnH2nBr2,  heated  with  water  and  lead 
oxide,  yield  glycols  or  oxides  at  the  same  time  as  aldehydes 
and  ke tones.  In  certain  cases  this  may  be  explained  by  the 
fixation  of  water  to  the  acetylene  products  which  are  at  first 
formed.  In  this  manner  ethylene  bromide  is  converted  into 
aldehyde.  The  conversion  of  the  bromide  of  trimethyl-ethylene 

(CH3)2.CBr  (CH3)2.CH 

into  the  ketone 
CH3.CHBr  CH3.CO 

can  also  be  explained  by  the  fixation  of  water  to  the  unsat- 
urated  alcohol, 

(CH3)2.C 

II        , 
CH3.C.OH 

1  See  Jour.  Soc.  Phys.  Chim.  Kusse,  vol.  19,  pp.  414  and  553;  vol.  20,  p.  518. 


ISOMERIZATION.  219 

which  is  at  first  formed,  and  the  subsequent  splitting-off  of 
water.  But  the  same  explanation  cannot  be  used  in  the  case 
of  the  transformation  of  the  bromide  of  di-isopropyl, 

(CH3)2.CBr  (CH3)3.C 

|      ,  into  the  ketone  |    . 

(CH3)2.CBr  CH3.CO 


v 

The  conversion  of  phenyl-ethylene  oxide,  V)  into 

CH2/ 

phenyl-acetaldehyde,  C6H5.CH2.CHO,  by  boiling  with  a  20  per 
cent,  solution,  of  sulphuric  acid,  or  by  the  action  of  acetyl 
chloride  or  benzoyl  chloride,  is  also  a  fixation  and  removal 
of  water. 

In  the  same  manner,  symmetrical  diphenyl-ethylene  oxide, 


,  with  dilute  sulphuric  acid  at  200°  C.,  is  converted 
C6H5.CH 
into  diphenyl-acetaldehyde,  (C6H5)2CH.CHO. 

(C6H5)2.CX 
oxBenzene  pinacoline,  |  \0,  is  converted  into  the  /? 

(CflHfi)2.C/ 

compound,  (C6H5)3C.CO.C6H5,  when  it  is  heated  to  150°  C. 
with  hydrochloric  or  hydrobromic  acids.1 

Compounds  containing  nitrogen  often  give  rise  to  cases  of 
isomerization.  When  ammonium  cyanate  is  heated  it  gives 
urea;  2  the  substituted  ureas  and  the  thio-ureas  may  be  obtained 


1  A.  Zagumenny,  On  the  Aromatic  Pinacones  and  Pinacolines,  St.  Petersburg, 
1881  (in  Russian). 

2  The  synthesis  of  urea  can  be  regarded  as  the  dissociatibn  of  ammonium 
cyanate   into   cyanic  acid,  CO:NH,  and  ammonia,  which  then  recombine  in  a 
different  manner: 

CO :  NH+  NH3=  CO^**2* 

\1N  ii, 

Inversely,  urea,  heated  in  a  sealed  tube  with  alcoholic  potash,  gives  cyanic 
acid  and  ammonia. 


220  ORGANIC  SYNTHESES. 

in  the  same  manner.  The  esters  of  true  cyanic  acid  heated  to 
200-210°  C.  are  converted  into  the  isocyanic  esters.  The 
phenylhydrazines,-  on  heating,  give  pyrazolines: 

CH.CH  i  CIi2       CH.CH2.CH2 

II  =   II  I 

NHNH.C6H5       N  -  N.C6H5 

The  isonitriles,  on  prolonged  heating,  are  changed  into  nitriles. 
Thus, 


heated  to  200°  C.,  is  converted  into  C6H5.CN. 

The  aromatic  ketoximes,  by  the  action  of  various  agents, 
yield  isomeric  anilides.  The  oxime  derivative  of  benzophenone, 
{C6H5)2C:N.OH,  dissolved  in  acetic  acid,  by  the  action  of 
gaseous  hydrochloric  acid  at  the  ordinary  temperatures,  is  con- 
verted into  benzanilide,  CeHs.CO.NH.CeHs. 

Azoxy  compounds  are  converted  into  oxy-azo  derivatives 
by  sulphuric  acid: 

C6H5.NX  C6H5.N 

l>  =  ||  . 

C6H5.N/         HO.C6H4.N 

The  isomerization  in  this  case  can  be  considered  as  the 
result  of  the  reaction  between  the  hydrate  of  diazobenzene, 
CeHsN'.N.OH,  or,  more  exactly,  its  sulphate,  and  phenol 
formed  by  the  decomposition  of  the  azoxy-benzene  by  the  sul- 
phuric acid. 

The  diazo-amido  compounds,  for  example, 

C6H5.N:N.NH.C6H5, 


yCII 

1  The  formula  for  this  body  as  given  by  Alexeyeff  is  C6H4<^  |  j    . 


ISOMERIZA  TION.  221 

are  converted  into  amido-azo  derivatives, 
C6H5.N:N.C6H4.NH2, 

by  a  prolonged  cooling  of  their  solutions,  but  more  readily  by 
the  action  of  aniline  hydrochloride  : 

C6H5.N  :  N.NH.C6H5+C6H5.NH2.HC1 


There  is  at  first  formed,  without  doubt,  diazobenzene  chloride, 
CeH5N  :N.C1,  and  aniline,  which  subsequently  react  with  each 
other. 

When  the  secondary  aromatic  amines  are  heated  they  are 
converted  into  the  primary;  the  tertiary  into  the  second- 
ary, etc.  Thus,  the  iodomethylate  of  dimethyl  aniline, 
C6H5.N(CH3)3l,  at  220-230°  C.,  gives  the  hydriodide  of  di- 
methyl toluidine: 

CH3.C6H4.N(CH3)2.HI; 

and  the  latter,  heated  still  higher,  gives  hydriodide  of  methyl- 
xylidine, 

(CH3)2.C6H3.NH(CH3).HI; 

and  at  335°  C.  there  is  formed  the  hydriodide  of  trimethyl- 
amido-benzene  : 

(CH3)3.C6H2.NH2.HI. 

This  isomerization  may  be  explained  by  a  dissociation  of  the 
ammonium  derivative  and  the  action  of  RI  on  the  compound. 
The  R  group  takes  the  ortho  or  para  position  with  reference 
to  the  nitrogen,  but  never  the  meta. 


222  ORGANIC  SYNTHESES. 

Pyridine  compounds  behave  in  the  same  manner  when 
heated:  C5H5N.C2H5I,  heated  to  320°  C.  for  some  hours,  is  con- 
verted into  the  hydriodide  of  ethylpyridine,  C5H4(C2H5)N.HI. 
This  method  is  applied  to  the  preparation  of  the  homologues 
of  pyridine. 

Isomerization  affords  a  method  for  the  synthesis  of  the 
diamine  derivatives,  starting  from  the  hydrazo  compounds.1 
Thus,  hydrazobenzene, 

C6H5.NH 

I     , 
C6H5.NH 

under  the  influence  of  acids,  gives  benzidine: 

C6H4.NH2 


In  the  same  manner,  hydramines,  heated  to  130°  C.,  or  by 
boiling  with  potash,  are  converted  into  a  stable  nucleus : 


C6H5.CH:NX  C6H5.C.NH 

>CH.C6H5.  || 

C6H5.CH:N/  C6H5.C.NH 


k  C6H5.C.NtL 

>CH.C6H5.  ||         >CH.C6H5. 

.0 V  C6H5.C.NH/ 

Hydrobenzamide.  Amarine. 


An  interesting  fact  is  the  reciprocal  transformation  by 
heat  of  the  two  isomers  of  dichlortolane,  using  63°  and 
143°  C.: 

C6H5.C.C1 
C6H5.C.C1* 

1  By  the  action  of  energetic  reducing  agents  on  azo  bodies,  which  give  hydrazo- 
compounds,  the  latter  isomerizing  as  above. 


ISOMERIZATION.  223 

This  isomerization,  along  with  others  (fumaric  and  maleic 
acids,  etc.),  can  only  be  explained  by  considering  the  spatial 
relations  of  the  atoms  in  the  molecule,  and  by  admitting,  with 
Wislicenus,  that  one  of  the  isomers  is  piano-symmetrical  and  the 
other  axio-symmetrical.1  In  these  cases,  as  with  dichlortolan?,, 
where  two  different  bodies  are  represented  by  the  same  formula, 
the  isomerization  is  called  tautomerism.  When  one  and  the 
same  body  is  decomposed  differently  under  the  influence  of 
different  chemical  agents,  a  single  formula  does  not  suffice  to 
explain  its  reactions;  two  formulas  are  required,  giving  a  different 
distribution  of  the  atoms  in  their  spatial  relations  in  the  mole- 
cule. Thus,  aceto-acetic  ester,  C3H.CO.CH2.CO.OR,  under 
certain  conditions  behaves  like  a  compound  having  the  formula, 
CH3.C(OH):CH.CO.OR. 

Phloroglucol  (trioxy-benzene  1:2:4)  sometimes  behaves  as  a 
triketone : 

CO 
HzC/NcHa 

OCX/ CO  * 
CH2 

Optically  inactive  substances  (but  containing  an  asym- 
metric carbon  atom)  can  be  converted  into  different  isomers 
by  different  decompositions.  The  simple  crystallization  of  the 
salts  is  sometimes  sufficient,  as  in  the  case  of  tartaric,  malic, 
phenylglycollic  acids,  etc.  In  the  same  manner,  artificial  a- 
propylpyridine  (the  salt)  gives  an  isomer  which  rotates  the 
plane  of  polarized  light  to  the  right. 

This  double  nature  appears  to  disappear  when  one  or  several 
isomers  are  mixed  together,  when  the  different  rotatory  powers 
mutually  annul  one  another. 

The  splitting-up  of  a  substance  into  two  isomeric  bodies 
may  sometimes  take  place  through  the  agency  of  a  micro-organ- 
ism which  will  destroy  one  of  the  isomers.  Thus,  with  amyl 

1  See  Butt.  Soc.  Chim.,  vol.  49,  p.  457. 


224  ORGANIC  SYNTHESES. 

alcohol,  CH(CH3)(C3H7)OH,  there  is  formed,  by  the  aid  of  fer- 
ments, a  Isevo-gyrate  alcohol.  Glyceric  acid, 

CO.OH 
CH.OH  , 
CH2.OH 

behaves  in  the  same  manner.  With  conicine,  there  cannot  be 
obtained  by  this  method  the  optically  active  isomers,  on  account 
of  its  destructive  action  on  inferior  organisms. 


INDEX 


A. 

PAGE 

Acetal 1 159 

preparation  of 164 

Acetamide 175 

Acetanilide 1 70 

Acetic  acid,  removal  of 126 

Aceto-acetic  acid 144 

Aceto-acetic  ester 107 

Aceto-anthramine 175 

Aceto-chlor-hydrin 161 

Aceto-ethyl  mercaptol 166 

Acetone 189 

Aceto-nitrile 103 

Aceto-oxalic  ester 199 

Aceto-phenone 70,  145 

Acetoxime 160 

Acetyl  chloride 40,  75 

Acetyl-para-toluidine,  oxidation  of 17 

Acetylene  hydrocarbons,  isomerization  of 218 

tetrabromide 202 

/3-Acetyl-propionic  acid 44 

Acid  amides,  action  of  bromine  on 74 

conversion  of,  into  acids 43 

NH2  group  in 42 

chlorides 160 

group,  effect  of,  on  oxidations 1 8 

nitriles,  preparation  of 207 

reducing  agents,  action  of,  on  azo-bodies 63 

«  Acids,  esters  of 113 

Acids,  reduction  of 51 

Acrolein -ammonia 119 

Adipic  acid 211 

Air,  oxidizing  action  of 1 1 

225 


226  INDEX. 

PAGE 

Alanine 96 

Alcohols,  oxidation  of,  to  aldehydes 12,  25 

reaction  of,  with  amines 169 

reduction  of 55 

removal  of 127 

Aldehydes 1 50 

chlor-substituted 53 

condensation  of 191 

nitration  of 87 

oxidation  of 5,12,23 

reaction  of,  with  amines 171,  172 

reduction  of ." 53, 

Aldehydine 172 

Aldol 136 

Aldoximes 92,117 

Aliphatic  amines,  separation  of 93 

Alkamines 119 

Alkylamines 119 

Allophanic  esters 152 

Allyl  alcohol,  oxidation  of 9 

benzene 201 

chloride 201 

cyanide. 1 54 

dimethyl-carbinol 189 

iodide 76,  1 32 

thio-urea 46 

Allylene 1 56 

Amarine,  oxidation  of 26 

Amides  of  di-acids,  conversion  of,  into  salts 43 

Amidines 140 

Amido-acetamide 94 

Amido-aceto-phenone 198 

Amido-acids 167 

Amido-ammonium  salts 43 

/9-Amido-butyric  acid 140 

Amido-compounds,  nitration  of 86 

Amido-ethers,  decomposition  of 44 

Amido-group,  substitution  of 58 

Amido-oximes 140 

Amido-sulphonic  acids 102 

Amines,  action  of  halogens  on 74 

chlorine  derivatives  of 40 

nitrites  of 41 

of  the  paraffin  series 41 

removal  of 127 

Ammo-acids 124 


INDEX.  227 

PAGE 

Ammonia-aldehydes 198 

Ammonia  derivatives,  preparation  of 93 

fixation  of 139,  148 

removal  of 1 20 

Ammoniacal  chloride  of  zinc 195 

Ammonium  derivatives 167 

Amyl  alcohol 50,  224 

Amylene 1 50 

Anhydrides,  preparation  of 162 

reaction  of,  with  amines 171 

Anilides 147 

Aniline 73 

oxidation  of 10 

reduction  of 50 

Anthramine 96,  175 

Anthraquinone 142 

oxime 92 

Anthrol 96 

Antipyrine 77 

Aromatic  aldehydes,  oxidation  of 24 

reduction  of 53 

amines,  separation  of 94 

compounds,  condensation  of,  with  acids 198 

oxidation  of 7 

hydrocarbons,  action  of  halogens  on 69 

nitration  of 85 

Aromatic-hydroxy  acids,  removal  of  water  from 114 

nitriles 117 

Asparagine i38 

Aspartic  acid 62 

Atropic  acid 1 31 

Aurine 97 

Azines 173 

Azo-benzene 60 

oxidation  of 35 

Azo-compounds 62,  1 78 

oxidation  of , 35 

Azo-phenylene 169 

Azoxy-benzene 60 

Azoxy -compounds 1 80 

B. 

Benzaldehyde 53 

Benzaldehydine J 72 

Benzaldoxime l6° 


228  INDEX. 

PAGE 

Benzene  disulphonic  acid 45 

hexahydride,  derivatives  of 61 

oxidation  of 20,  35 

a-Benzene-pinacoline 219 

Benzene  ring,  replacement  of  halogen  by  OH  in 38 

Benzene-sulphinic  acid 139 

Benzhydrol 80,  162 

Benzidine 222 

Benzoates,  formation  of 184. 

Benzo-hydroxy-meta-carboxylic  acid 54 

Benzoin 56 

Benzonitrile 207 

Benzophenone 55,  99,  212 

Benzophenone-meta-carboxylic  acid 54 

Benzoquinone-oxime 93 

Benzoyl-acetic  acid 200 

Benzoyl-acrylic  acid 145 

Benzoyl-benzoic  acid 200 

Benzoyl  chloride 40,  80 

Benzoyl-f ormic  ester 44 

Benzyl-acetamide 1 70 

Benzyl-acetic  acid * 144. 

Benzyl-aceto -acetic  acid 144. 

Benzyl  alcohol 55 

amine 53. 

cyanide 91,  205 

ether 55 

iodide 89 

Benzylidene-acetone,  oxidation  of 1 1 

Benzylidene  chloride,  oxidation  of 37 

Bisulphites,  fixation  of 139 

Borneol 1 50 

Brom-acetic  acid 75 

Brom-anthraquinone 39 

Brom-benzyl  bromide 206 

Brom-ethyl  acetate 89 

Brom-ethylene I31 

Brom-naphthylamine 164 

Brom-nitrobenzene 94 

Brom-nitro-benzoic  acid 65 

Brom-nitro-ethane 89 

a-Brom-/?-nitro-naphthalene 64 

Brom-nitro-naphthalene 64. 

Brom-nitro-toluene - 69 

/?-Brom-propionic  acid 89 

Brom-succinic  ester l  *& 


INDEX.  229 

PAGE. 

Brom-tri-brom-phenol 218 

Bromine,  fixation  of 133 

oxidizing  action  of 1 1 

removal  of no 

substitution  of  by  chlorine 74 

by  iodine 76 

Butylamine,  normal 41 

secondary 41 

Butyric  acid,  oxidation  of 15 


C. 

Camphoric  acid,  constitution  of 21 

Caproic  acid,  oxidation  of 33 

Carbamic  acid 140 

Carbohydrates 147 

Carbon  dioxide,  fixation  of 183 

disulphide 140 

reaction  of,  with  amines 174 

monoxide,  fixation  of 182 

removal  of 122 

tetrabromide 175 

tetrachloride 175 

Carbonic  acid,  removal  of 123 

Carbonyl  chloride 160,  168 

Carboxyl-ketonic  acids 107 

Carboxylic  acids,  nitration  of 86 

reaction  of,  with  amines 1 70 

synthesis  of 210 

Carbylamine,  preparation  of 207 

Caustic  potash,  action  of  in  oxidations 114 

CH  group,  conversion  of  into  C.OH 19 

oxidation  of 19,  20 

CH.CH  group,  conversion  of,  into  CO.CO 20 

CH2  group,  conversion  of,  into  CO 19 

oxidation  of 19 

CH3  group,  conversion  of,  into  CO.OH 16 

conversion  of,  into  CHO 15 

oxidation  of 15,  16 

oxidation  of,  in  phenols 17 

CH2OH  group,  conversion  of,  into  CHO 23 

CH2.OH  group,  oxidation  of 22 

Chlor-acetamide 94 

Chlor-acetic  acid 75 

Chlor-acetic-anilide 1 70 


230  INDEX. 

PAGE 

Chlor-acetic-ester 78 

Chlor-aldehyde 191 

Chlor-benzene 68 

Chlor-dinitro-benzene 95 

Chlor-dinitro-phenol 39 

Chlor-ethyl-acetate 94 

Chlor-formic  acid 160 

Chlor-iodo-ethylene 89 

Chlor-malyl  chloride 8 1 

Chlor-nicotinic  acid 57 

Chlor-nitrobenzene 94 

Chlor-nitrotoluidine 95 

Chlor-platinate  salts 77 

«-Chlor-propionic  acid 109 

a-Chlor-quinoline 39 

/5-Chlor-quinoline 40 

7--Chlor-quinoline 40 

Chlor-sulpho-cymene 57 

Chloral 53 

Chlorine,  fixation  of 132 

formation  of  compounds  of 35 

removal  of .  109 

substitution  of,  by  bromine 75 

substitution  of,  by  fluorine 77 

substitution  of,  by  iodine 75 

Chlorine  derivatives,  conversion  of,  into  iodine  compounds 76 

Chloroform 145 

CHO  group,  oxidation  of 23 

substitution  of,  by  CH3 53 

CH.OH  group,  oxidation  of 21 

Choline.  .- i,  23 

Chromic  acid,  action  of,  in  oxidations 13 

mixture 13 

Chromyl  chloride,  action  of,  in  oxidations 13 

preparation  of 1 6 

Chrysoidine 178 

Cinnamic  acid 191,  192 

oxidation  of 30 

Cinchomeronic  acid ". 66 

Citric  acid 144 

CO  group,  conversion  of,  into  CH2 54 

into  CH.OH 53 

into  C.OH 53,  187 

Collidine : .  . .  .  119 

Combustion 15 

Condensation  with  loss  of  water 191 


INDEX.  231 

PAGE 

Conicine 224 

oxidation  of 25 

Copper  spiral,  action  of,  in  oxidation 1 1 

Coumaric  acid 114 

Coumarine 136,  193 

Cresol,  oxidation  of 14 

Croton  aldehyde 136 

Crotonic  acid 140,  194 

oxidation  of 9 

aldehyde 119,  191 

Cumalic  acid 214 

Cuminic  acid,  oxidation  of 219 

alcohol 55 

Cyanimide » 155 

Cyanethine 216 

Cyanhydrins 96,  187 

Cyanic  acid 151 

Cyanides,  oxidation  of 25 

Cyanogen 137,  154 

chloride 138 

Cyan-phenine 216 

Cyanuric  acid 215 

ester 215 

Cymene 55 

oxidation  of 8,  18 

D. 

Desoxalic  acid 123,  215 

Desoxybenzoin 56 

Dextrose 161 

Diamido-anthraquinone 97 

Diamidogene 63 

Diamido-imido-fluorescein 98 

Diamines,  derivatives  of 176 

Dianthramine 1 75 

Diazo-acetic  acid 200 

ester 78 

Diazo-acids 119 

esters  of 44 

Diazo-amido  compounds 59.  *77 

Diazo-benzene-sulphonic  acid 100 

Diazo-chlorides 59 

group,  substitution  of 58 

Dibenzyl,  oxidation  of 10,  25 

Di-brom-nitro-ethane 91 


232  INDEX. 

PAGE 

Dibrom-propionic  acid,  oxidation  of 37 

Dibrom-toluene,  oxidation  of 38 

Dichlor-nitrobenzene 39 

a-Dichlor-propionic  acid,  oxidation  of 37 

Dichlor-propionyl  chloride 95 

Dichlor-tolane 222 

Diethylamine 121 

Di-imides,  derivatives  of 1 76 

Di-isopropyl  bromide 219 

Diketones 142 

Dimethyl-acetamide 43. 

Dimethyl-acetylene 218 

Dimethyl-amido-benzoic  acid 204. 

Dimethyl-aniline 83,  204. 

Dimethyl-ethyl-carbinol,  oxidation  of 29 

Dimethyl-nitramine 43 

Dimethyl-toluidines 83 

/3-Dinaphthylamine 96 

Dinitrobenzoic  acid 65 

Dinitro  compounds,  preparation  of 89 

Dinitro-ethane 89 

Dinitro-mesitylenic  acid 85 

Dinitro-stilbene 211 

Dinitro-toluene 65 

Dinitro-toluidine,  oxidation  of 117 

Dioxy-acetophenone 198 

Diphenic  acid 115 

Diphenyl 212 

oxidation  of 34 

Diphenyl-ethane 196 

Diphenyl-methane 55,  202 

Diphenyl-propane 201 

Diphenyl-succinic  acid 206 

Diphenyl-thiourea 1 74 

Direct  oxidation  with  decomposition  of  molecule 29 

Dithio-carbamic  acid 121 

Dithionic  acid 47 

Divanillin 213 

Durol 218 

E. 

Elements  capable  of  oxidation 2 

Erythrine  tetrachloride 80 

Erythrite .  80 

oxidation  of 22,  29 


INDEX.  235 

PAGE 

Esters,  formation  of 158 

saponification  of 146 

Ether 158 

Bthers,  formation  of 162 

Ethyl  acetate 145 

Ethyl-acetylene 218 

Ethyl  alcohol,  action  of  chlorine  on 73 

amine !" 58,  74,  75 

Ethyl-benzene 67 

oxidation  of 1 8,  1 9,  34 

Ethyl  bromide 68 

oxidation  of 36 

Ethyl-chlor-formate 211 

Ethyl-ether,  oxidation  of 1 1 

Ethyl  iodide 88,  103 

Ethyl-isobutyl  ketone,  oxidation  of 32 

Ethyl-nitro-acetate 89 

Ethyl-nitrolic  acid 91 

Ethyl  oxalate 199 

Ethyl  peroxide,  formation  of 25 

Ethylene  bromide 74 

chlor-bromide 75 

chloride 75 

oxidation  of 37 

diamine 120 

oxide 55,  1 1 1 

perchloride no 

Ethylidene  bromide ./. 159 

chloride 67 


F. 

Fatty  acids,  dry  distillation  of  silver  salts  of 33 

reaction  of,  with  halogens 68 

Fluorescein 97,  98 

Fluorine  compounds,  preparation  of 78 

Formaldehyde,  preparation  of 1 1 

Formamide 43 

Formaniline 49 

Formic  acid 144 

removal  of 1 26 

Fumaric  acid no,  145 

oxidation  of 28 

Fumaryl  chloride 8 1 


234  INDEX. 

G. 

PAGB 

Gallic  acid 1 25,  2 1 3 

Glacial  acetic  acid 163 

Glucose 176 

Glucosides 147 

Glyceric  acid 79,  224 

Glycerol,  oxidation  of 11,12 

Glycocoll 124 

Glycol 80,  113 

oxidation  of 31 

Glycollic  acid 179 

Glycols,  anhydrides  of 187 

removal  of  water  from 113 

Glyoxal,  oxidation  of 24 

reaction  of,  with  amines 173 

Glyoxime 92 

Glyoxylic  acid 145 

Guanidine,  conversion  of,  into  urea 44 

Guanidines 98 


H. 

Halogen,  removal  of 109 

substitution  of,  by  HS 100 

byNH2 93 

by  N.OH 91 

by  NO2 88 

by  O.NO 89 

by  O.NO2 90 

by  SO2.OH 103 

by  sulphur 09 

Halogen  acid,  removal  of no 

carriers 7° 

compounds,  preparation  of 70 

reduction  of 48 

group,  substitution  of,  by  hydroxyl 8 1 

Halogens,  substitution  of 56 

Hexachlor-benzene,  oxidation  of 38 

Hexaethyl  chloride I IO 

Hexoxy-benzene I  8  3 

«-Hexyl  iodide,  oxidation  of 36 

Hydration J42 

Hydrazines •  •   59,  66 

oxidation  of 27 

substituted *?6 


INDEX.  235 

PAGE 

Hydrazobenzene 49,  222 

Hydrazo  derivatives,  oxidation  of 26 

Hydriodic  acid  as  a  reducing  agent 49,  52 

removal  of in 

Hydro-atropic  acid 205 

Hydrobromic  acid,  removal  of in 

Hydrobenzamide 172 

Hydrobenzoin 185 

Hydrocarbon,  removal  of 126 

Hydrochloric  acid,  removal  of no 

Hydrocollidine-dicarboxylic  acid 198 

Hydrocyanic  acid 187 

Hydrogen  additive  aromatic  compounds,  oxidation  of 34 

fixation  of 60 

substitution  of,  by  a  metal ic  6 

by  N.OH 93 

by  NO2  group 85 

by  SO2.C1 105 

by  SO2.OH 101 

Hydrogen  peroxide,  fixation  of 139 

sulphide,  fixation  of 139 

removal  of 1 20 

Hydrophthalic  acid 1 26 

Hydropyridine  compounds,  oxidation  of 25 

Hydroquinone 54,  159,  213 

Hydrosorbic  acid,  oxidation  of 14 

f-Hydroxy-acids 114 

Hydroxy-acids 1 24 

Hydroxy-anthraquinone 197 

Hydroxy-azobenzene 179 

Hydroxy-benzoic  acid,  condensation  of 2C  o 

Hydroxy-benzoin 56 

Hydroxybenzoyl-benzoic  acid 197 

Hydroxyl  oxygen,  reduction  of 48 

substitution  of,  by  NH2 95 

by  NH.R 97 

for  halogen 35 

Hydroxylamine  derivatives,  preparation  of 82 

Hypochlorous  acid,  fixation  of 141 

I. 

Imides 138 

Imido  esters 149 

Indirect  oxidation 35 

Iodides,  methods  of  oxidizing 36 


236  INDEX. 

PAGE 

lodination 72 

Iodine,  fixation  of 134 

removal  of no 

substitution  of,  by  bromine 76 

by  chlorine 75 

by  fluorine 77 

by  hydrogen 56 

Iodine  trichloride 71 

lodo-acetic  acid 79 

lodo-aniline 74 

lodo-benzene 89 

lodo-ethyl  alcohol 89 

lodo-ethylene 89 

/?-Iodo-propionic  acid 211 

lodo-stearic  acid in 

Jodoform 50,  75 

Iso-butyl  iodide,  oxidation  of 36 

Iso-butylene 1 36 

oxidation  of 30 

Iso-butyric  acid,  oxidation  of 19 

aldehyde 1 86 

Iso-caproic  acid 114 

Iso-cyanic  esters 140,  151 

Iso-dialuric  acid 173 

Iso-dibrom-succinic  acid 126 

Iso-glucosamine 178 

Iso-nitriles 1 38,  2  20 

Iso-nitro-aceto-acetic  ester 90 

Iso-nitro-propane 82 

Iso-nitroso-ketones 91 

Iso-nitroso-malonic  ester 90 

7-Iso-nitroso-valeric  acid 44 

Iso-phthalophenone 204 

Isoprene 215 

Iso-propyl-benzene 201 

Iso-propyl-bromide 58 

Iso-propyl-chloride 58,  67 

Jso-propyl-dimethyl-carbinol,  oxidation  of 29 

Iso-propyl-iodide,  oxidation  of 36 

Iso-sulpho-cyanides 121, 140,  153 

Isomerization 217 


INDEX.  237 

K. 

PAGB 

Keto-amides 43 

Ketones,  condensation  of 192 

nitration  of 97 

oxidation  of 5,  32 

reduction  of 53 

Ketonic  acids 54,  125,  144 

aldehydes,  reduction  of 56 

oxygen,  reduction  of 48 

Ketoximes 92 


L. 

Lactic  acid 54 

Laevulose 176 

Laevulinic  acid 114 

M. 

Malic  acid 81 

Malonic  ester 146 

Manganese  dioxide,  action  of,  in  oxidation 12 

Mellitic  acid 123 

Mercaptans 165 

Mesityl  oxide 145 

Mesitylene 192 

oxidation  of 19 

Meta-chlor-benzoic  acid,  oxidation  of 38 

Meta-chlor-phenol 41 

Metacrylic  acid 113 

Meta-nitro-benzoic  acid 69 

Meta-phenylene  diamine 178 

Metallic  salts  of  organic  acids 106 

Metallo-organic  derivatives,  preparation  of 106 

Meta-styrol 215 

Methyl-acetamide 43 

Methyl  amine 93 

Methyl-butyl-ketone,  oxidation  of 33 

Methyl-formamide 170 

Methyl-malonic  acid 123 

Methylene  iodide 5° 

Milk  sugar,  oxidation  of * n 

Mixed  ethers 158 

Mono-chlor-acetic  acid,  oxidation  of 37 

Muscarine l 


238  INDEX. 


N.    - 

PAGE 

Naphthalene,  oxidation  of 34 

^-Naphthylamine 64,  96 

NH  group,  substitution  of ,  by  S 100 

conversion  of,  into  0 44 

NH2  group,  displacement  of,  by  OH 41 

joined  to  CO,  conversion  of,  into  OH 43 

method  of  preventing  oxidation  of 17 

substitution  of,  by  halogen 77 

by  HS loo 

byN02 87 

by  SO.2OH 104 

Nicotinic  acid 57,  125 

Nitric  acid,  action  of,  in  oxidations 14 

derivatives,  preparation  of 82 

Nitrile  radical,  substitution  of 58 

Nitriles 136,  140 

conversion  of,  into  esters 44 

polymerization  of 216 

Nitrites  of  secondary  amines 1 18 

Nitro-compounds,  bromination  of 71 

reduction  of 48,  63 

separation  of,  from  nitrous  esters 88 

substitution  of 58 

Nitro-amido-benzoic  acid 118 

Nitro-anilides 86 

Nitro-benzene 70 

action  of  bromine  on 71 

Nitro-benzyl  alcohol 197 

Nitro-carboxylic  acids 124 

Nitro-chlor-benzene 39 

Nitro-dichlor-benzene 100 

Nitro-naphthalene •„ 122 

a-Nitro-naphthalene 102 

Nitro-nitriles,  reduction  of 65 

Nitro-phenols , 96 

Nitro-phthalene 122 

Nitroso-phenyl-urea 138 

Nitro-styrol 85 

Nitro-sulphonic  acids 85 

Nitro-toluene,  oxidation  of 13,  18 

Nitrolic  acids 82 

Nitrosamines 83 

reduction  of 63 

Nitroso-anilide 84 


INDEX.  239 

PAGE. 

Nitroso-anilide,  reduction  of 64 

Nitroso  compounds,  reduction  of 63 

Nitroso-dimethyl-aniline 58,  83, 

Nitroso  group,  substitution  of 58- 

Nitrosyl  chloride,  fixation  of 141 

Nitrous  acid,  action  of,  on  aliphatic  alcohols 84- 

on  imido  compounds 84 

on  nitro-compounds 82 

derivatives,  preparation  of 82 

N : N  group,  conversion  of,  into  H.OH 44. 

substitution  of,  by  halogens 78- 

N.OH  group,  conversion  of,  into  0 43 

NO2  group,  influence  of 39 

Normal  propyl  bromide 201 

O. 

Octyl  bromide 210 

CEnanthol 191 

(Enanthylic  acid,  oxidation  of 33. 

aldehyde 151 

OH  group,  conversion  of,  into  H 55 

introduction  of,  with  silver  salts 37 

substitution  of,  by  halogen 79 

by  SO«H - 104 

Oleic  acid 135 

oxidation  of 28- 

Ortho-amido-anilides 117 

Ortho-iodo-phenol,  oxidation  of 3& 

Ortho-nitro-benzal-acetone,  oxidation  of 10 

Ortho-nitro-phenol 39 

Ortho-nitro-toluene 64 

Ortho-oxy-benzoic  acid 46 

Ortho-sulpho-amido-toluene 116 

Ortho-toluene-sulphonic  acid 46 

Ortho-toluic  acid,  oxidation  of 17 

Oxamic  acid 171 

Oxamide 171 

Oxidants,  action  of 10- 

Oxidation  as  result  of  condensation 9 

direct 15 

methods  of  conducting 8- 

phases  of 2 

with  ammonia  derivatives 41 

Oxidizing  agents,  action  of 8,  1 1 

Oximes 62- 


240  INDEX. 

PAGE 

Oxy-acids,  action  of  phosphorus  pentachloride  on 8 1 

formation  of 185 

nitration  of.  ..." 87 

Oxy-anthraquinone 39 

a-Oxy-carboxylic  acids 113 

a-Oxy-iso-butyric  acid 144 

^x-Oxy-nitriles,  reaction  of,  with  amines 169 

Oxy-pyridine 55 

Oxy-pyrone 98 

Oxygen,  action  of 1 1 

fixation  of 131 

removal  of 60 

substitution  of 60 

by  I2 82 

by  NH 97 

by  N.OH 92 

by  sulphur 99 

in  CO  group ....,* 81 


P. 

Palmitolic  acid,  oxidation  of 28 

Para-amido-benzoic  acid 167 

Para-amido-phenol,  oxidation  of 26 

Para-brom-aniline '. 69 

Para-chlor-ortho-toluidine 64 

Para-nitro-aniline 42 

Para-nitro-benzyl  chloride 90,  211 

Para-nitro-phenyl-propiolic  acid 133 

Para-nitro-toluene 69,  7 1 

Paraldehyde 151 

Para-phenylene  diamine,  oxidation  of 26 

Para-rosaniline,  formation  of 10 

Penta-methylene-diamine 1 20 

Phenanthraquinone-oxime 92 

Phenates 184 

Phenazine 69 

Phenol 68,  69 

acid  esters  of 105 

action  of  bromine  on 73 

Phenol-aldehydes 193 

Phenol  bromide 57 

Phenol,  ethers  of 163 

Phenols,  making  of 41 

nitration  of 96 


INDEX.  241 

PAGE 

Phenols,  oxidation  of 14,  20 

reaction  of,  with  amines 169 

reduction  of 55 

Phenol-sulphonic  acid 46 

Phenyl-aldehyde 1 44 

Phenyl-brom-acetic  acid 20  5 

Phenyl-carbimide 168- 

Phenyl-chloroform,  oxidation  of 67 

Phenyl-cyanate 215 

Phenyl-ethylene  oxide 113 

Phenyl-glycidic  acid 125 

Phenyl-glycocoll 1 70 

Phenyl-glycol 113 

Phenyl-hydrazine 1 76 

Phenyl  iodide 132 

Phenyl-lactic  acid 144 

Phenyl-pyrazol 176 

Phenyl-urea 175 

Phloroglucic  acid 125 

Phloroglucol 125,  223 

Phorone 192 

Phosphonium  iodide 50 

Phosphorus  halides,  use  of 80 

Phosphorus,  use  of,  with  hydriodic  acid 49 

Phthalic  anhydride 196 

Phthaleins 55 

Phthalimide,  reduction  of 53 

Phthalophenone 204 

Phthalyl-acetic  acid 194 

Phthalyl  chloride 204 

Picoline '. 119 

Piperidine,  oxidation  of 25 

Piperonal 122 

Platinum  spiral,  action  of,  in  oxidations 1 1 

Polyhydric  phenols,  oxidation  of 20 

Polymerization 215 

Potash,  fusions  with 38 

Potassium  permanganate,  action  of,  in  oxidations 12 

persulphate 1.05 

Primary  alcohols,  oxidation  of 5 

amines,  action  of  heat  on 175 

oxidation  of 26 

nitro  compounds 91 

Propane,  oxidation  products  of 6 

Propargylic  alcohol .  159 

Propylene  bromide 58 


242  ^  INDEX. 

PAGE 

Propylene  chloride 58 

a-Propylene  chloride 132 

Propyl-phenyl-ketone,  oxidation  of 16 

Propyl-pseudo-nitrol 83,  1 31 

Protocatechuic  aldehyde 122 

Pseudo-cumene,  oxidation  of i  & 

Pseudo-nitrols 82 

Pyrazolines 62,  220 

Pyrazols 62 

Pyridine-carboxylic  acids 125 

Pyridone  derivatives 97 

Pyrocatechin 169 

Pyrogallol 125 

Pyromellic  acid 123 

Pyromucic  acid 198 

Pyrone 97 

Pyrotartaric  acid 215 

Pyruvic  acid 54,  112 


Q. 

Quinic  acid,  oxidation  of 34. 

Quinoline 55 

carboxylic  acid 125 

oxidation  of 34. 

Quinone 54 

Quinone-dioxime 93. 

Quinone-oximes 92,  1 32 

Quinone,  reduction  of 53 

Quinoxalines 173 


R. 

Radicals  capable  of  oxidation 2 

Reducing  agents,  action  of 49 

Reduction,  different  forms  of 48 

Removal  of  halogens 109 

hydrogen 109 

oxygen 109 

Resorcin 163,  213 

oxidation  of 14,  20 

Rhodamine 97 

Rhodizonic  acid 183 


INDEX.  243 


S. 

PAGE 

Salicyl  aldehyde 192 

anilide 86 

Salicylic  acid 87,  194 

Secondary  alcohols,  Chancel's  reaction  for 89 

oxidation  of 5 

hydrocarbons,  substitution  of ,  by  Cl 67 

Side-chains,  influence  of  position  of,  on  oxidation 7 

oxidation  of 7 

Silver  oxide,  action  of,  in  oxidations 12 

ammoniacal  solution  of 12 

Simple  ethers,  removal  of 127 

Skraup's  synthesis 214 

Sodium  acetanilide 184 

amalgam 50 

as  a  reducing  agent 50 

stannite 5 

Soluble  starch,  action  of  oxidants  on 12 

SO2.OH  group,  substitution  of,  by  OH 105 

Stannous  chloride  as  a  reducing  agent 51 

Styrol 215 

Substituted  acids,  replacement  of  halogen  by  OH  in 38 

Substituents  of  the  first  group 68 

second  group 68 

Substitutions,  laws  of 67 

Succinamide 1 20 

Succinic  anhydride c 150 

Succinimide 1 20 

Succinyl  chloride 52 

oxalic  acid 199 

Sulph-acetic  acid 103 

Sulphine  acids 60 

Sulphinic  acid 139 

Sulphocyanic  acid 153 

Sulpho-mesitylenic  acid 185 

Sulphonal ! 166 

Sulphones 101,  166 

Sulphonic  acid  group,  conversion  of,  into  OH 45 

substitution  of 60 

Sulphonic  acids,  action  of  bromine  on 174 

amides  of 43 

chlorides  of 40,  57,  95,  161 

fusion  of,  with  caustic  potash 45 

lead,  salts  of 45 


244  INDEX. 


Sulphur,  displacement  of,  by  O  ........................  .  .........  ,  .  46 

preparation  of  compounds  containing  .......................  165 

substitution  of  ...........................................  60 

by  NH  ...................................  9& 

Sulphuric  acid,  esters  of  ...........................................  105 

fixation  of  .........................................  139 

anhydride,  fixation  of  ....................................  1  39 

removal  of  ...................................  121 

Sulphurous  anhydride,  fixation  of  ..................................  139 

Sulphuryl  chloride  ................................................  105 

Synthetic  sugar  ..................................................  22 


T. 

Tartaric  acid 81,  215 

Tartronic  acid 124,  146 

Tautomerism 225. 

Terebenthene,  oxidation  of 20 

Terpene 141 

Tertiary  alcohols,  oxidation  of 5, 

preparation  of 190- 

amines 155 

amyl  iodide,  oxidation  of 36 

Tetrabrom-phenol 2 1  & 

a-Tetrahydro-naphthylamine,  oxidation  of 35 

Tetramethyl-benzene 2i& 

Tetramethyl-diamido4-fluorescein 97 

Thio-amides 98- 

Thio-anilides. 99 

Thio-benzanilide 99 

Thio-butyric  acid 120 

Thio-carbamic  acid 121 

Thiophene 119 

Thiophenyl-urea 46 

Thio-urea 98,  128: 

substituted 1 20- 

Thymol 1 26 

Tin  as  a  reducing  agent 51 

Toluene 70 

oxidation  of 1 1 

Triacetonamine 119* 

Triacetonine 119 

Triamido-azo-benzene 179* 

Tribrom-phenol 57 

bromide 57 


INDEX.  «45 

PAGR 

/?-Trichlor-acetyl-acrylic  acid 145 

Trichlor-lactic  acid,  oxidation  of 37 

Trichlor-phenol 104. 

Triethyl-phosphine 215 

Triethyl-sulphuric  iodide 156 

Trimethyl-carbinol,  oxidation  of 29 

Trimethylene no 

Trimethyl-ethylene  bromide 218- 

Trimethyl-rosaniline 97 

Trinitro-mesitylene 65 

Triphenyl  -brom-methane 36 

Triphenyl-chlor-methane 202 

Triphenyl-guanidine 1 74 

Triphenyl-methane 202 

oxidation  of 20- 

Triphenyl-urethane 197 


U. 

Unsaturated  acids,  synthesis  of 192 

alcohols,  oxidation  of 27 

compounds,  oxidation  of 14 

groups,  reduction  of 48 

hydrocarbons,  oxidation  of 27 

Uramido-benzoic  acid 175 

Urea 164 

synthesis  of 219 

Urethanes 152 

Uric  acid,  oxidation  of 31 


V. 

Valerianic  acid 211 

Valeric  acid 215 

Valero-lactone 114 

Valerylene 215 

Vanillin 213 

oxidation  of 24 


W. 

Water,  fixation  of 135 

removal  of 112 


246  INDEX. 


X. 

PACK 

Xylene 71 

hexahydride,  oxidation  of 25 


Z. 

Zinc  as  a  reducing  agent 51 

dust  as  a  reducing  agent 51 

ethyl 132 

propyl 190 


X^BR^lrxN 

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